Mutation carriers genes modifier. Medical search. Frequent questions

Background: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. (eur.nl)
In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. (eur.nl)
T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. (eur.nl)
This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.Conclusions and inteNo evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. (eur.nl)
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers. (ox.ac.uk)
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. (ox.ac.uk)
We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. (ox.ac.uk)
We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P -8, at 5 loci, which are not associated with risk in the general population. (ox.ac.uk)
These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. (ox.ac.uk)
In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). (escholarship.org)
AbstractIntroductionSeveral common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. (escholarship.org)
MethodsTo evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12599 BRCA1 and 7132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. (escholarship.org)
rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR=0.81, 95%CI: 0.74-0.90, P-trend=4x10^-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR=0.78, 95%CI:0.62-1.00, P-trend=0.049). (escholarship.org)
ConclusionsThe present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. (escholarship.org)
We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. (escholarship.org)
Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. (escholarship.org)
To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. (escholarship.org)
Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. (escholarship.org)
This association was absent in BRCA2 carriers (p = 0.57). (escholarship.org)
Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. (escholarship.org)
Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. (escholarship.org)
Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. (escholarship.org)
The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. (escholarship.org)
Mutations of BRCA1 or BRCA2. (escholarship.org)
Dr. Offit discussed international efforts to study these risk modifiers and plans for a clinical trial in BRCA2 mutation carriers to test how knowledge of modifying mutations will impact patient treatment decisions and outcomes. (bcrf.org)
Mutations in the BRCA1 and BRCA2 genes are highly prevalent in Ashkenazi Jews, but genetic screening is typically only recommended for those with a family history of cancer. (bcrf.org)
Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. (amsterdamumc.org)
A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. (amsterdamumc.org)
In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. (amsterdamumc.org)
The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. (amsterdamumc.org)
Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients. (cdc.gov)
A review of data from 3184 BRCA1 and 2157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 documented elevated risk of male breast cancer associated with pathogenic variants of BRCA1 (relative risk [RR] 4.30), and especially with pathogenic variants of BRCA2 (RR = 44.0). (medscape.com)
[ 8 ] Other studies have found that men who carry BRCA2 mutations are at 80-fold higher risk of developing breast cancer compared with men in the general population, that breast cancer develops in up to 1 in 10 male BRCA2 carriers, and these cases may be more aggressive than sporadic cases. (medscape.com)
BRCA2 and CHEK2 were the most frequently mutated genes (in 11.0 and 4.1% of patients, respectively) and pathogenic variants in BRCA2 , CHEK2 , and PALB2 were associated with significantly increased risk. (medscape.com)
Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). (uni-koeln.de)
P-trend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. (uni-koeln.de)
The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers. (uni-koeln.de)
Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers. (uni-koeln.de)
Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers. (uniklinikum-dresden.de)
Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. (unimib.it)
We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. (unimib.it)
Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. (elsevierpure.com)
To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. (elsevierpure.com)
HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). (elsevierpure.com)
SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). (elsevierpure.com)
SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). (elsevierpure.com)
These data on modifiable characteristics from a large group of young carriers of BRCA1 or BRCA2 mutations represent a unique resource for advancing our knowledge about breast cancer prevention in premenopausal women at high risk for the disease. (cancer.gov)
Diagnostic chest X-rays and breast cancer risk before age 50 years for BRCA1 and BRCA2 mutation carriers. (cancer.gov)

About 50 common variants have been shown to modify BC risk for mutation carriers. (ox.ac.uk)
Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. (ox.ac.uk)
The LRRK2 gene has rare (p.G2019S) and common risk variants for Parkinson's disease (PD). (ucl.ac.uk)
VAMP4 is in close proximity to DNM3, and was associated with PD in a recent study, so it is possible that variants in this gene may be important. (ucl.ac.uk)
The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence the severity of familial CCM1 disease, as manifested by ICH and greater brain lesion count.METHODS:Hispanic CCM1 patients (n=188) harboring the founder Q455X 'common Hispanic mutation' (CHM) in the KRIT1 gene were analyzed at baseline. (kaiserpermanente.org)
We analyzed 830 variants in 56 inflammatory and immune response genes for association with ICH and residuals of log-transformed total or large lesion count adjusted for age at enrollment and gender. (kaiserpermanente.org)
Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. (unimib.it)
Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. (unimib.it)
In a review of germline multi-gene panel testing (MGPT) in 715 male breast cancer patients, 18.1% tested positive for variants in 16 breast cancer susceptibility genes. (medscape.com)
Average age at diagnosis was 54 years in patients with CHEK2 1100delC, compared with 62 years in patients without pathogenic variants and 64 years in carriers of all other pathogenic variants. (medscape.com)
Nowadays, it is still unclear as to the number of genes or their variants that are necessary for effective screening. (mdpi.com)
This paper describes the development of a carrier screening custom panel for cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss consisting of 116 variants in the CFTR , PAH , SERPINA1, and GJB2 genes. (mdpi.com)
Multifactor dimensionality reduction indicated that the best genetic model for classical onset group versus controls involved the APCS gene, whereas for late-onset cases, one APCS variant (APCSv1) and two RBP variants (RBPv1 and RBPv2) are involved. (psu.edu)
High serum ferritin levels are seen in hyperferritinemia cataract syndrome associated with pathogenic variants in the FTL (ferritin L-chain) gene. (mhmedical.com)
The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. (biomedcentral.com)
It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). (biomedcentral.com)
Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms, translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately finding disease-modifying therapies for neurodegenerative disorders. (biomedcentral.com)
RA: In reviewing a genetic database of 'healthy' individuals that serve as research controls, I found that it contained many variants on the FBN1 gene that are considered to be 'pathogenic' variants that cause Marfan syndrome. (f101g.org)
Guillaume Smits (GS): The discovery of apparently healthy individuals (or individuals with such low penetrance of the disease that they are unaware of being ill) with pathogenic variants raises the possibility that they are genetically protected from even the most severe forms of Marfan syndrome by the action of a so-called protective gene that can counteract the failure of the FBN1 gene that causes the disease. (f101g.org)
Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. (unimib.it)
The results of this study lead us to reject the three alternative hypotheses of (1) a highly penetrant, major prostate cancer-susceptibility gene at 17p11, (2) the allelic variants Leu217 or Thr541 of HPC2/ELAC2 as high-penetrance mutations, and (3) the variants Leu217 or Thr541 as low-penetrance, risk-modifying alleles. (johnshopkins.edu)
The early essentiality of the PIGA gene, its location on the X chromosome, and the complex interactions between PIGA variants and disease modifiers conspire to create a sphinx-like disease. (substack.com)
Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. (cdc.gov)
Genetic variants of the phenylalanine hydroxylase gene in patients with phenylketonuria in the northeast of Iran. (cdc.gov)
Diagnosis is by sweat test or identification of 2 cystic fibrosis-causing gene variants in patients with a positive newborn screening test result or characteristic clinical features. (msdmanuals.com)
CFTR variants can involve frameshift (a deletion or insertion in a DNA sequence that shifts the way a sequence is read) or nonsense (stop) mutations. (msdmanuals.com)
A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility. (who.int)

Interestingly, the first genome-wide CRISPR interference/activation screens to discover susceptibility genes of oxidative stress in induced pluripotent stem cell (iPSC)-derived human neurons identified PSAP. (nature.com)

To test this, we studied the relationship between the CYP1B1 Asn453Ser ( N453S ) genetic polymorphism and FPAH penetrance in BMPR2 mutation carriers 19 . (ersjournals.com)
A total of 41 -thalassaemia carriers and 40 control subjects without haemoglobinopathies were screened for the C282Y, H63D and S65C mutations by polymerase chain reaction-restriction fragment-length polymorphism. (who.int)
Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. (cdc.gov)

We analyzed alleles of candidate genes encoding non-fibrillar components of TTR amyloid deposits and a molecule metabolically interacting with TTR [retinol-binding protein (RBP)], for possible associations with age of disease onset and/or susceptibility in a Portuguese population sample with the TTR V30M mutation and unrelated controls. (psu.edu)
Rarely, women with pathogenic mutations on both alleles of the gene have been reported. (institut-vision.org)

In the clinical setting these genetic characteristics can become problematic and making predictions of carrier status and severity of the disease impossible to predict. (wikipedia.org)
As usual, there was a vast array of PD research presented, covering topics that included clinical trials, epidemiology, non-pharmacologic interventions, non-motor symptoms, neuroimaging, gene- and cell-based therapies and more. (apdaparkinson.org)
The heterogeneous risk among carriers suggests other genetic modifiers could exist.MethodsWe analysed clinical, genotype and gene expression data derived from paediatric ACC, R337H carriers, and adult ACC patients. (ox.ac.uk)
Methods and results: We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. (unimib.it)
however, carriers of the same mutation exhibit variability in penetrance and clinical expression. (psu.edu)
A third gene variant (S65C) may lead to increased serum iron and ferritin levels without clinical significance (type 1c). (mhmedical.com)
Although SOD1 mutations have been identified in many western populations at comparable frequencies, screening in clinical practice suggests that these mutations are rare in The Netherlands. (bmj.com)
We discuss the underlying mechanisms, clinical implications, and the challenges associated with deciphering the contribution of multiple genes in the development and manifestation of such disorders. (e-kjgm.org)
PIGA mutations observed in boys fall on a spectrum of clinical severity from infant mortality to survival to adulthood. (substack.com)
Remarkably, the top hit reinforces a clinical finding from 2013 in one of the first papers to describe boys with PIGA mutations and a new disease called Ferro-Cerebro-Cutaneous syndrome - later renamed PIGA-CDG. (substack.com)
We will focus on carriers under age 50 years at diagnosis (cases) or interview (controls) who have participated in an international Collaborative Family Registry for Breast Cancer Studies (CFRBCS) and in clinical studies in New York, Ontario and Australia. (cancer.gov)
Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. (medscape.com)
Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. (medscape.com)
In sickle cell trace, the heterozygosis for genes of normal (HbA) and mutant (HbS) hemoglobins (AS genotype) does not exhibit clinical symptoms of the disease under physiological conditions 3,5 . (bvsalud.org)
Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)

Objective To estimate the frequency of SOD1 mutations in a large referral cohort of familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS) patients from The Netherlands and to compare this frequency with that of other developed countries. (bmj.com)
METHODS: We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). (ox.ac.uk)

We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. (escholarship.org)
We restricted our analyses to single nucleotide polymorphisms (SNPs) previously identified in GWASs to associate with disease or human traits.ResultsA SNP, rs971074, in the alcohol dehydrogenase 7 gene significantly and reproducibly associated with allelic differences in ACC age-of-onset in both cohorts. (ox.ac.uk)
Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). (elsevierpure.com)

BACKGROUND:Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions that often result in intracerebral hemorrhage (ICH), seizures, and neurological deficits. (kaiserpermanente.org)
Familial pulmonary arterial hypertension (FPAH) is caused, in 80% of families, by autosomal dominant mutations in the gene encoding bone morphogenetic protein receptor type 2 ( BMPR2 ). (ersjournals.com)
The hairless variant is inherited in an Autosomal Dominant fashion meaning only one copy of the FOXI3 gene variant is required to produce hairlessness. (pawprintgenetics.com)
Hemochromatosis is an autosomal recessive disease caused in most cases by a pathogenic variant in the HFE gene on chromosome 6. (mhmedical.com)
Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson's disease (PD). (sdbonline.org)
PME4 is largely inherited in an autosomal recessive manner, though there are reports of heterozygous carriers showing mild PME4 phenotypes (Hopfner et al. (preventiongenetics.com)
Dominant negative mutations (where mutation on one copy renders the other copy inactive) are involved in osteogenesis imperfecta type I and autosomal dominant nephrogenic diabetes insidipus . (dorak.info)
Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)

The observation of pleiotropy has emerged, with mutations in the same gene giving rise to diverse phenotypes, which further increases the complexity of phenotype-genotype correlation. (biomedcentral.com)
After crossing mice expressing the Cre recombinase under the hindbrain driver (En1) with the inducible knock-in mouse model, results showed a selectively expressed DYT1 genotype in the hindbrain and normal torsin A gene in the forebrain structures. (tylershope.org)
Familial Mediterranean fever in the Syrian population: gene mutation frequencies, carrier rates and phenotype-genotype correlation. (muzoktcrb.ru)
Sickle cell anemia (SCA) is the most common and severe form of SCD, resulting from genetic inheritance of HbS genes from both progenitors (SS genotype) 1 . (bvsalud.org)

Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. (uthscsa.edu)
We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. (uthscsa.edu)
Overall, the data suggest that genomic variation at multiple loci that encode proteins that interact biologically with BRCA1 are associated with modified breast cancer and ovarian cancer risk in women who carry BRCA1 mutations. (uthscsa.edu)
Mutations in genes that encode structural proteins of the cardiac sarcomere are the more frequent genetic cause of HCM. (bvsalud.org)
The Parkinson's disease genes pink1 and parkin , which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. (sdbonline.org)

Paediatric ACC is frequently associated with TP53 mutations, with particularly high incidence in Southern Brazil due to the TP53 p.R337H (R337H) germline mutation. (ox.ac.uk)
New mutations do occur in about 32% of cases, and germline mosaicism is not uncommon. (medscape.com)

abstract = "It has been more than a decade since heterozygous loss-of-function mutations in the progranulin gene (GRN) were first identified as an important genetic cause of frontotemporal lobar degeneration (FTLD). (elsevierpure.com)
ABSTRACT A case-control study aimed to determine the prevalence of C282Y, H63D and S65C mutations of the HFE gene in -thalassaemia carriers and investigate their influence on iron absorption. (who.int)

Mutations in bone morphogenetic protein receptor type 2 ( BMPR2 ) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. (ersjournals.com)
However, it is unclear why BMPR2 mutations have reduced penetrance, and why, after puberty, females with mutations are about 2.5-fold more likely to develop FPAH than males 1 . (ersjournals.com)
Recently, our studies of BMPR2 mutation carriers implicated altered oestrogen metabolism as a key factor in the penetrance of FPAH in females. (ersjournals.com)
Points to Consider Regarding Risk-Reducing Mastectomy in High-, Moderate-, and Low-Penetrance Gene Carriers. (cdc.gov)
If we could have access to genomic data of people with pathogenic mutations in whom the penetrance of the disease is low, we could use the bioinformatics tools developed with Professor Tom Lenaerts to identify a possible protective gene. (f101g.org)
Considering the impact of genetic heterogeneity, phenocopies, and incomplete penetrance on the linkage and association studies of prostate cancer and on the power to detect linkage and association in our study sample, our results cannot rule out the possibility of a highly penetrant prostate cancer gene at this locus that only segregates in a small number of pedigrees. (johnshopkins.edu)
In single gene disorders (as opposed to multifactorial-complex disorders), the mutation's population frequency is low, its penetrance is high, and the contribution of environment is lower with notable exceptions of PKU and few others. (dorak.info)

A paired box gene 6 ( PAX6 ) missense mutation, p.T391A, has been described in a patient with bilateral ONA, nystagmus, and normal anterior eye segments. (molvis.org)

A number of factors make the identification of the genetic defects underlying human ectrodactyly a complicated process: the limited number of families linked to each split hand/foot malformation (SHFM) locus, the large number of morphogens involved in limb development, the complex interactions between these morphogens, the involvement of modifier genes, and the presumed involvement of multiple gene or long-range regulatory elements in some cases of ectrodactyly. (wikipedia.org)
We identified 11q22.3 as a new modifier locus in BRCA1 carriers. (escholarship.org)
The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10-8DHFR p=8·37 × 10-7 MTRNR2L2 p=2·15 × 10-9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10-4DHFR p=8·45 × 10-4MTRNR2L2 p=1·20 × 10-3). (ox.ac.uk)

Conclusions The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. (bmj.com)
Linkage analysis in 18 familial ALS pedigrees associated the gene encoding Cu/Zn superoxide dismutase ( SOD1 ) on chromosome 21 to the syndrome. (bmj.com)
We report the frequency of SOD1 mutations in a large Dutch referral population of sporadic and familial ALS patients, and a comparison is made with other countries by reviewing studies on SOD1 mutation frequencies in populations from Europe, USA and Japan. (bmj.com)
Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. (muzoktcrb.ru)

An uncommon juvenile-onset variant that is characterized by severe iron overload, cardiac dysfunction, hypogonadotropic hypogonadism, and a high mortality rate is usually linked to a variant gene on chromosome 1q designated HJV that produces a protein called hemojuvelin (type 2a) or, rarely, to a variant of the HAMP gene on chromosome 19 that encodes hepcidin (type 2b). (mhmedical.com)
The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10-10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. (ox.ac.uk)
Lowe syndrome is caused by an inherited mutation in the OCRL gene, mapped to chromosome Xq 26.1, which encodes the OCRL1 protein. (medscape.com)
Disease burden is suffered specifically by boys because of a cruel twist of fate: the PIGA gene happens to reside on the X chromosome. (substack.com)
As we all learned in primary school biology class, boys have just one copy of every gene on the X chromosome. (substack.com)
In Cri-Du-Chat syndrome (5p deletion), the genetic basis of the phenotype is haploinsufficiency for the telomerase reverse transcriptase gene ( TERT ), which is included in the deleted part of chromosome 5. (dorak.info)
The responsible gene has been localized on the long arm of chromosome 7. (msdmanuals.com)

We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. (unimib.it)
Polymorphisms in modifier genes have been shown to lead to a high iron phenotype. (mhmedical.com)
The traditional paradigm monogenic disorders, also known as Mendelian disorders, are characterized by the presence of mutations in a single gene that contribute to the development of a specific phenotype or disease. (e-kjgm.org)
Traditionally, monogenic disorders have been considered as relatively straightforward genetic conditions, where a mutation in a single gene is sufficient to cause the observed phenotype. (e-kjgm.org)
Digenic inheritance refers to the involvement of mutations in two genes to manifest a particular phenotype or disease. (e-kjgm.org)
With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. (biomedcentral.com)
Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. (ox.ac.uk)
Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. (medscape.com)

It is noted a wide interindividual variety of disease severity that has been suggested as result of polymorphisms in several genes 12 , mainly of fetal hemoglobin which has been pointed as a target for promising treatments 13 . (bvsalud.org)

The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women. (elsevierpure.com)

The BRCA genes are the most commonly mutated genes in hereditary breast cancer, but the types of mutations and their impact on risk vary widely. (bcrf.org)
Mutations in NALP12 cause hereditary periodic fever syndromes. (muzoktcrb.ru)

Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene, presence of modifier genes, and oligogenic inheritance. (biomedcentral.com)

In people with CF, mutations in the CFTR gene (cystic fibrosis transmembrane conductance regulator gene) cause the CFTR protein to not work correctly. (inogen.com)
The origin of cystic fibrosis is genetic in nature and requires two abnormal CF genes. (inogen.com)
Sometimes cystic fibrosis occurs without a known family history because anyone with a single abnormal CF gene is a carrier. (inogen.com)

Each of us inherits hundreds of genetic mutations from our parents, as they did from their forebears. (dorak.info)

HFE gene mutation (usually C282Y/C282Y) is found in most cases. (mhmedical.com)
The C282Y gene variant and hemochromatosis are uncommon in Black and Asian American populations. (mhmedical.com)
H63D, S65C and C282Y allele frequencies were 30.5%, 13.4% and 7.3% respectively in -thalassaemia carriers and 10.0%, 2.5% and 0.0% respectively in the control group. (who.int)
RÉSUMÉ La présente étude cas-témoins visait à déterminer la prévalence des mutations C282Y, H63D et S65C du gène HFE chez les porteurs d'une -thalassémie et à rechercher leur influence sur l'absorption du fer. (who.int)
Au total, 41 porteurs d'une -thalassémie et 40 sujets témoins ne présentant aucune hémoglobinopathie ont participé à cette étude visant à examiner les mutations C282Y, H63D et S65C du gène HFE par la méthode du polymorphisme de longueur des fragments de restriction d'ADN amplifié. (who.int)

Monogenic disorders are traditionally attributed to the presence of mutations in a single gene. (e-kjgm.org)
However, recent advancements in genomics have revealed instances where the phenotypic expression of apparently monogenic disorders cannot be fully explained by mutations in a single gene alone. (e-kjgm.org)
In these cases, a specific mutation or set of mutations in a single gene can be directly linked to the development of the disorder. (e-kjgm.org)
While monogenic disorders were traditionally attributed to mutations in a single gene, there is increasing evidence to suggest that the phenotypic expression of some apparently monogenic disorders cannot be fully explained by mutations in a single gene alone. (e-kjgm.org)
Most single gene disorders can be investigated by prenatal diagnosis using DNA extracted from cells obtained from amniocentesis at 16-18 weeks' gestation or chorionic villus sampling (CVS) at about 10-12 weeks' gestation. (dorak.info)

The consent application GEMS App allows anyone with Marfan syndrome to actively participate in research by joining the GEMS study which aims to identify protective modifier genes in the context of cardiovascular damage in Marfan syndrome. (f101g.org)

In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. (escholarship.org)
ResultsOnly SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele Hazard Ratio (HR)= 0.87, 95%CI:0.81-0.94, P-trend=3x10^-4). (escholarship.org)
BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. (escholarship.org)
Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. (escholarship.org)
We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10 -6 ). (escholarship.org)
In recent years, scientists have uncovered many less common gene mutations associated with breast cancer, and work by Dr. Kenneth Offit and others suggests that many of these act to modify risk (either increasing or decreasing it) when combined with BRCA or other mutations. (bcrf.org)
Drs. Mary-Claire King , Ephrat Levy-Lahad and Moein Kanaan , who collaborate on international studies in Israel, the United States and the Palestine Authority, presented findings that suggest that population-wide screening for BRCA mutations in Ashkenazi Jews-including the novel method of screening men in families without a known history of cancer-will identify high-risk women who wouldn't otherwise be screened. (bcrf.org)
Because risk factors, both modifiable (weight and other lifestyle choices) and non-modifiable (age, family history or inherited genes) vary widely, prevention needs to be individualized. (bcrf.org)
Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. (amsterdamumc.org)
Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. (amsterdamumc.org)
Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. (amsterdamumc.org)
Aims: In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. (unimib.it)
Whole-Genome Sequencing Identifies PPARGC1A as a Putative Modifier of Cancer Risk in BRCA1/2 Mutation Carriers. (cdc.gov)
Impact: The combined application of these and other recently identified genetic risk modifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers. (uni-koeln.de)
H63D homozygotes do not develop hemochromatosis but may be at increased risk for amyotrophic lateral sclerosis, and carriers may be at increased risk for non-cardia gastric cancer. (mhmedical.com)
Nor can we rule out a prostate cancer-modifier gene that confers a lower-than-reported risk. (johnshopkins.edu)
Additional larger studies are needed to more fully evaluate the role of this gene in prostate cancer risk. (johnshopkins.edu)
We will use unconditional logistic regression to estimate odds-ratios relating these attributes to breast cancer risk while controlling for potential confounders, and use robust variance estimators to account for any correlation present in attributes of related carriers. (cancer.gov)
It is also estimated that each human being is a carrier of around five recessive lethal genes and perhaps even more recessive disease genes, which may pose risk for the offspring of related individuals (such as cousin marriages). (dorak.info)
Carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene increases the risk of obesity in infants with phenylketonuria. (cdc.gov)

Results One novel mutation (p.I99V) and a homozygous p.D90A mutation were identified in SALS patients. (bmj.com)
However, we did observe a trend of higher Leu217 homozygous carrier rates in patients than in control subjects. (johnshopkins.edu)
However, since the discovery of homozygous GRN mutations in patients with a lysosomal storage disorder, investigation into the possible roles of PGRN and its proteolytic cleavage products granulins, in lysosomal function and dysfunction, has taken center stage. (elsevierpure.com)

PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy. (cdc.gov)

The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR=0.82, 95%CI:0.74-0.90, P-trend=3.1x10^-5, P-difference=0.03). (escholarship.org)
Mutations found in methyl CpG binding protein 2(MECP2) are associated with Rett syndrome. (cms.gov)
The HFE protein is thought to play an important role in the process by which duodenal crypt cells sense body iron stores, and the variant gene leads to increased iron absorption from the duodenum. (mhmedical.com)
CF gene mutations are divided into classes based on how damaged the CFTR protein function is. (inogen.com)
Sickle cell disease, also known as sickle cell anemia, is an inherited blood disorder caused by a mutation in the gene responsible for producing hemoglobinâ the protein in red blood cells that carries oxygen throughout the body. (aplagen.com)
In hypermobility type of Ehlers-Danlos syndrome , haploinsufficiency (where one copy is unable to produce the protein in sufficient quantity) due to a 30-kb deletion of tenascin-X (TNXB) gene is responsible for the disease. (dorak.info)

This indicates that the genetics of hairy hairless Chinese Crested dogs is not completely understood and there are likely other modifiers in the genome that interact with this gene. (pawprintgenetics.com)

point stop mutations), hemophilia ( A , B ), phenylketonuria -PKU (point mutation), Duchenne muscular dystrophy (DMD) , adenosine deaminase (ADA) deficiency causing severe combined immune deficiency (SCID), Tay-Sachs disease (hexosaminidase A deficiency). (dorak.info)

The identified mutation for SHSF syndrome (split-hand/split-foot syndrome) a duplication on 10q24, and not a mutation of the tp63 gene as in families affected by EEC syndrome (ectrodactyly-ectodermal dysplasia-cleft syndrome). (wikipedia.org)
In 1992, Nussbaum and colleagues reported that mutations of OCRL1 caused the rare X-linked disorder oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome, which includes the diagnostic triad of congenital cataracts, neonatal or infantile hypotonia with subsequent mental impairment, and renal tubular dysfunction. (medscape.com)
Membrane trafficking defects caused by mutation in OCRL may explain renal tubular defects observed in Lowe syndrome, including the inability of proximal tubular cells (PTC) to reabsorb low-molecular weight (LMW) proteins and other solutes such as phosphorus and bicarbonate from the glomerular filtrate. (medscape.com)
An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. (muzoktcrb.ru)

DNM3 has previously been reported as a genetic modifier of the age at onset in PD patients carrying the LRRK2 p.G2019S mutation. (ucl.ac.uk)
Thus, although the TTR V30M mutation is required for the disease in Portuguese patients, different genetic factors may govern the age of onset, as well as the occurrence of anticipation. (psu.edu)

Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. (escholarship.org)

In 2011, a novel mutation in DLX5 was found to be involved in SHFM. (wikipedia.org)

Genomewide copy number screening using microarray-based comparative genomic hybridization (arrayCGH) revealed a microdeletion of 10q23.33q23.33, potentially implicating the cytochrome p450, subfamily XXVIA, polypeptide 1 ( CYP26A1 ) and cytochrome p450, subfamily XXVIC, polypeptide 1 ( CYP26C1 ) genes encoding retinoic acid (RA)-degrading enzymes as novel candidate genes for ONA. (molvis.org)

This SNP resides in a gene involved in the retinoic acid (RA) pathway and patients with differing levels of RA pathway gene expression in their tumours associate with differential ACC progression.ConclusionsThese results identify a novel genetic component to ACC development that resides in the retinoic acid pathway, thereby informing strategies to develop management, preventive and therapeutic treatments for ACC. (ox.ac.uk)

In addition, gene expression data implicating the oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. (ersjournals.com)
The excess of adult females suggests oestrogen as a possible disease modifier, as does a lower prevalence among pre-pubertal females compared with males 2 , 3 . (ersjournals.com)
Thus some 20-60% of carriers live to advanced ages without developing the disease, which suggests that other genes or personal attributes may modify carriers' risks. (cancer.gov)

If expression of a trait requires only one copy of a gene (one allele). (msdmanuals.com)

It is a highly heterogeneous group of disorders, with more than 80 genes or loci implicated [ 3 ]. (biomedcentral.com)

Finally, we summarize new findings on profibrotic genes as well as genetic and non-genetic factors involved in the pathophysiology of HCM. (bvsalud.org)
These findings link a selective brain circuit abnormality to gene carrier status and demonstrate the similar effect of DYT1 mutatnt torsion A on humans and mice. (tylershope.org)

How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? (lu.se)
Resolving chromatin remodeling-linked gene expression changes at cell type resolution is important for understanding disease states. (simonsfoundation.org)
In addition, we examined the patterns of global gene expression of primary and immortalized RPTE and compared them with uncultured PT freshly dissociated from human kidney. (simonsfoundation.org)
However, the expression of most of these genes is absent or repressed in cultured RPTE. (simonsfoundation.org)
Rather, cultured RPTE exhibit a gene expression profile indicative of a stressed or injured kidney. (simonsfoundation.org)
In summary, this study demonstrated similar global gene expression patterns and responses to BKV infection between primary and immortalized RPTE. (simonsfoundation.org)
While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow-up, with a pattern resembling autoimmune or inflammatory disease. (simonsfoundation.org)
Attributed to the failure of neurons to clear dysfunctional mitochondria , loss of gene expression leads to loss of nigrostriatal neurons. (sdbonline.org)

Methods A total of 451 sporadic and 55 FALS patients were screened for SOD1 mutations. (bmj.com)
The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 ( PAX6 ) are known to be implicated in sporadic bilateral ONA. (molvis.org)

X-linked retinoschisis (XLRS) is an inherited retinal disorder caused by mutations in the RS1 gene and characterized by a splitting of the neural retina which will eventually lead to decrease vision. (institut-vision.org)
In Brazil, it's estimated the existence of more than 2 million carriers of the gene for HbS, with 700 to 1000 new cases of SCD every year, turning such disorder into a public health problem 6 . (bvsalud.org)

2 Subsequent studies have identified over 140 different SOD1 mutations in ALS patients. (bmj.com)

Loss of 50% of PIGA function is tolerated without disease, otherwise PIGA-CDG parents/heterozygous carriers would be sick. (substack.com)

Anatomy2

Organisms2

Diseases26

Chemicals and Drugs37

Analytical, Diagnostic and Therapeutic Techniques and Equipment31

Psychiatry and Psychology2

Phenomena and Processes62

Disciplines and Occupations2

Anthropology, Education, Sociology and Social Phenomena1

Information Science4

Named Groups2

Health Care13

Geographicals4

BRCA248

Variants27

Susceptibility genes1

Polymorphism3

Alleles2

Clinical15

Cohort2

Nucleotide3

Autosomal8

Genotype4

Encode5

Germline2

Abstract2

Penetrance7

Missense mutation1

Locus3

Familial4

Chromosome7

Phenotype8

Polymorphisms1

SNPs1

Hereditary2

Inheritance1

Cystic fibrosis3

Genetic mutations1

C282Y5

Single-gene5

Protective modifier genes1

Risk20

Homozygous3

Breast cancer1

Protein6

Genome1

Phenylketonuria1

Syndrome4

Onset2

Quantitative Trai1

Novel mutation1

Candidate genes1

Retinoic acid1

Suggests3

Allele1

Disorders1

Findings2

Expression8

Sporadic2

Disorder2

Studies have identified1

Heterozygous carriers1