Phenotype germ line mutation. Medical search. Frequent questions

Knowledge of the susceptibility genes underlying their phenotypes has provided additional information for the classification of these syndromes. (nih.gov)
Biallelic germline mutations in the mismatch repair genes MLH1 , MSH2 , MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). (bmj.com)
Heterozygous germline loss-of-function mutations of the genes encoding the crucial components of this MMR system ( MLH1 , MSH2 , MSH6 or PMS2 ) cause Lynch syndrome, a well characterised dominant cancer syndrome associated with hereditary non-polyposis colorectal cancer (HNPCC) and other malignancies (reviewed by Peltomaki 4 ). (bmj.com)
and (iv) genes harboring germline non-silent variants presumed to confer a risk of sporadic ALL. (haematologica.org)
Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
2) lilli mutation strongly suppresses the rough eye phenotype of ectopically expressed phyllopod (Tang, 2001), and (3) lilli was identified in a screen for genes that enhance the embryonic lethal phenotype of dpp alleles (Su, 2001). (sdbonline.org)
These mutant phenotypes correlate with markedly reduced expression of the early zygotic genes serendipity alpha , fushi tarazu and huckebein , which are essential for cellularization and embryonic patterning (Tang, 2001). (sdbonline.org)
In humans, mutations affecting the genes of this family are associated with specific diseases. (sdbonline.org)
1 Some of these, such as the MC1R 2 and ASIP 3 genes, have been fairly well studied and useful information has been obtained by examining mutation patterns at these loci. (creation.com)
Mutations in these genes affect proteins involved in the signaling pathway for pigment production and explain a large amount of the color variation in mammals. (creation.com)
These studies reveal that recurrent somatic mutations occur in only a handful of genes, with an overall mutational burden of roughly 1-2 per Mb. (springer.com)
CONCLUSIONS: In the absence of somatic copy number variations or mutations, the fully transformed phenotype of the MNTI may have arisen in infancy because of the combined effects of a germline CDKN2A mutation, tumor promoting somatic fusion genes and epigenetic deregulation. (ox.ac.uk)
About one third of patients with PGL have been reported to carry pathogenic germline variants in a growing list of susceptibility genes. (medscape.com)
Germline variants in the succinate dehydrogenase ( SDH ) genes are the most common genetic cause of PGLs, occurring in up to 15% of all patients with PGL and half of all familiar cases. (medscape.com)

NF2 patients who are treated at non-specialty centres have higher odds of death than those who are treated at specialty centres, and NF2 patients with missense mutations have lower odds of death than those with nonsense or frameshift mutations. (bmj.com)
7 Genotype-phenotype correlation studies have found that NF2 patients with constitutional NF2 missense mutations or large deletions generally have mild disease, those with splice site mutations have variable disease severity, and those with nonsense or frameshift mutations have severe disease. (bmj.com)
Based on an established filtering strategy and data analyses, along with confirmation by Sanger sequencing and co‑segregation, a novel frameshift mutation c.1317delA (p.Ala440LeufsTer14) in exon 10 of the APC gene was identified. (spandidos-publications.com)
This novel frameshift mutation causing FAP not only expands the germline mutation spectrum of the APC gene in the Chinese population, but it also increases the understanding of the phenotypic and genotypic correlations of FAP, and may potentially lead to improved genetic counseling and specific treatment for families with FAP in the future. (spandidos-publications.com)
Most of the mutations causing FAP are nonsense or frameshift mutations, and can result in premature stop codons thus produce truncated APC proteins ( 7 ). (spandidos-publications.com)
Patients with Frameshift mutation - or Nonsense mutations suffer poor prognosis. (wikidoc.org)

[ 9 ] No genotype-phenotype correlation has been found thus far. (medscape.com)
Students will understand the basis of genome maintenance and gene expression, and appreciate the concept of mutation at the level of the genotype and how this manifests at the phenotypic level. (manchester.ac.uk)
The goal of such comparisons of genotype and phenotype is to determine whether specific mutations cause respective combinations of symptoms. (wikidoc.org)

Conclusions: Patients with germline SMAD4 or BMPR1A mutations have a more prominent JP phenotype than those without, and SMAD4 mutations predispose to UGI polyposis. (elsevierpure.com)
Mutations in the Adenomatous polyposis coli (APC) gene are responsible for the majority of cases of FAP. (spandidos-publications.com)
In addition, it was correlated with extra‑colonic phenotypes featuring duodenal polyposis and sebaceous cysts in this family. (spandidos-publications.com)
Germline mutations in the tumor suppressor adenomatous polyposis coli gene (APC) on chromosome 5q22.2 are responsible for the most cases of FAP. (spandidos-publications.com)
MUTYH polyposis is caused by germline mutations of the MUTYH gene, a base excision repair gene. (msdmanuals.com)
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. (msdmanuals.com)

We are analysing alternative splicing and its association with germline variants and somatic mutations RNA and DNA sequencing data for thousands of women with sporadic or familial breast cancer. (lu.se)

Patients with Missense mutations have a better prognosis. (wikidoc.org)

Gene mutations: missense versus nonsense mutations, insertions, deletions and frameshifts. (manchester.ac.uk)

In the first family, we identified a pathogenic PMS2 mutation for which the affected patient was homozygous. (bmj.com)
Mice homozygous for the Thrb tm1Syc allele were mated to EIIa-Cre transgenic mice to generate mice that carry a germline deletion of the neomycin resistance gene. (jax.org)
Some of the stronger mutations cause a dominant white phenotype which is lethal in the homozygous condition. (creation.com)

In cases with Mutations in the splice-acceptor-region , there is no good correlation to determine. (wikidoc.org)

Results: Nine of 54 patients had germline SMAD4 mutations, 13 had BMPR1A mutations, and 32 had neither. (elsevierpure.com)
However, germline SMAD4 mutation, especially a well-described 4-bp deletion, can be used to confirm a clinical diagnosis of JPS. (nih.gov)

The focal dermal hypoplasia (FDH) genetic defect has been associated with at least 80 different mutations in the PORCN gene of the X chromosome (Xp11.23). (medscape.com)
Several lines of evidence indicate that there is a genetic predisposition to acute lymphoblastic leukemia (ALL), at least in a subset of cases. (haematologica.org)
Hopper JL, Dowty JG, Apicella C, Southey MC, Giles GG, Winship I. Towards more effective and equitable genetic testing for BRCA1 and BRCA2 mutation carriers . (cancervic.org.au)
Some mutations result in pleiotropy, although this is variable depending on genetic background, type of mutation, and location of the mutation. (creation.com)
Previously, creationist studies have pointed out the importance of evaluating genetic data to determine the types of mutations which have likely occurred throughout history. (creation.com)
There is no therapy for the underlying disorder of cell function caused by the genetic mutation. (wikidoc.org)
This suggests that recommendations for genetic counseling of at-risk relatives and stringency of surveillance for SDHA mutation carriers might need to be reassessed. (medscape.com)
Modern genomics methods produce vast amounts of genetic data, but we have limited ability to interpret the effects of sequence variation on gene expression, protein function and the individual's phenotype. (lu.se)

For humans, a maximum of 10 alleles could have made it through unless Noah's sons carried mutations. (creation.com)

Familial predisposition specific to leukemia is uncommon but has resulted in the identification of predisposing non-silent variants that are also observed in sporadic ALL cases, including TP53 germline mutations and low hypodiploid B-ALL, ETV6 variants and hyperdiploid ALL, and PAX5 mutations and B-ALL with dicentric/isochromosome 9. (haematologica.org)
10 Germline variants of IKZF1 are observed in familial B-ALL and immunodeficiency, 16 , 17 and somatic IKZF1 alterations are enriched in Philadelphia chromosome (Ph)-positive, Phlike, and DUX4 -rearranged B-ALL. (haematologica.org)

Denys-Drash syndrome is the result of mutations in the WT1 gene on chromosome band 11p13. (medscape.com)
Chromosomal mutations: changes in chromosome number or structure. (manchester.ac.uk)
Although mutation- or pathway-directed targeted therapy (e.g., using tyrosine kinase inhibitors to treat Philadelphia chromosome [Ph]-positive and Phlike B-cell-ALL) is currently available for only a minority of children with ALL, many of the newly identified molecular alterations have led to the exploration of approaches targeting deregulated cell pathways. (haematologica.org)
Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. (elifesciences.org)
There is a broad clinical spectrum known, but all patients checked have been found to have some mutation of the same gene on chromosome 22 . (wikidoc.org)

Denys-Drash syndrome (DDS) is a rare disorder consisting of the triad of congenital nephropathy, Wilms tumor , and intersex disorders resulting from mutations in the Wilms tumor suppressor ( WT1 ) gene. (medscape.com)
A germline mutation of CDKN2A and a novel RPLP1-C19MC fusion detected in a rare melanotic neuroectodermal tumor of infancy: a case report. (ox.ac.uk)
Exhaustive genomic, transcriptomic, epigenetic and pathological characterization was performed on the excised primary tumor and a derived cell line. (ox.ac.uk)
Whole-exome analysis of genomic DNA from both the tumor and blood indicated no somatic, non-synonymous coding mutations within the tumor, but a heterozygous, unique germline, loss of function mutation in CDKN2A (p16(INK4A), D74A). (ox.ac.uk)
Consistent with the melanotic phenotype of the tumor, elevated expression of tyrosinase was observed. (ox.ac.uk)

Mutations that disrupt the second alternative splicing site of the WT1 gene alter the normal ratio of KTS-positive/negative isoforms from 2:1 to 1:2 and result in abnormalities in glomerular formation and gonadal differentiation seen in Frasier syndrome. (medscape.com)
lilli mutations disrupt the transvection-dependent dpp phenotype and are also dominant maternal enhancers of recessive embryonic lethal alleles of dpp and screw . (sdbonline.org)

A spectacular example of this approach to treatment of breast cancer is application of a poly (ADP-ribose) polymerase (PARP) inhibitor, such as olaparib, to patients with germline BRCA1 mutations [4, 5]. (termedia.pl)

In the skin, these abnormalities follow the embryonic lines of Blaschko. (medscape.com)
lilli zygotic mutant embryos exhibit a partially ventralized phenotype similar to dpp embryonic lethal mutations (Su, 2001). (sdbonline.org)

All patients met the Manchester clinical diagnostic criteria for NF2 5 or had identified constitutional NF2 mutations. (bmj.com)
There are only a few reports on the expression of Ku70/80 in breast cancers [17-21], but the association of this protein with germline CHEK2 mutations in breast cancer patients is unknown. (termedia.pl)
However, although ER positive tumors tend to have a better prognosis in unselected breast cancer patients, germline CHEK2 mutations are associated with increased risk of the development of ER positive breast cancer with an unfavorable prognosis [24-26]. (termedia.pl)
11 ] demonstrated a substantial overall survival (OS) benefit in patients with PD-L1-positive (PD-L1 + ) metastatic or inoperable locally advanced TNBC through the addition of the anti-PD-L1 agent atezolizumab to first-line chemotherapy with nab-paclitaxel. (biomedcentral.com)
Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B -related nonsyndromic intellectual disability. (biomedcentral.com)
Many patients with NF II were included in studies that were designed to compare disease type and progression with exact determination of the associated mutation. (wikidoc.org)
Germline SDHA analysis was performed in 393 patients with genetically unexplained PGL. (medscape.com)
Germline SDHA mutations are relatively common (7.6%) in patients with genetically unexplained PGL. (medscape.com)
[ 15 , 16 ] In this study, we performed a nationwide evaluation of germline SDHA analyses undertaken in patients with PGL and characterized the clinical manifestations and disease penetrance in 30 index SDHA mutation carriers and their relatives. (medscape.com)

These two phenotypic classes appear to reflect variation inherent to the lilli loss-of-function phenotype, rather than partial rescue by a paternal copy of lilli , since they are similarly observed whether wild-type or heterozygous lilli males are used. (sdbonline.org)

NF-2 may be inherited in an autosomal dominant fashion, as well as through random mutation. (wikidoc.org)

It has been suggested that PTEN mutation-positive CS and BRR should be grouped as a single entity for clinical purposes and classified as the 'PTEN hamartoma-tumour syndrome' [111]. (nih.gov)
The purpose of the present study was to report the clinical features of a Chinese family with FAP and screen for novel mutations using the targeted next‑generation sequencing technology. (spandidos-publications.com)
These results suggest, that probably other factors (Environment, other mutations) will determine the clinical outcome. (wikidoc.org)
Current clinical understanding of germline SDHA mutation carriers is limited. (medscape.com)
To estimate the contribution of SDHA mutations in PGL and to assess clinical manifestations and age-related penetrance. (medscape.com)
SDHA mutation detection yield, clinical manifestations, and SDHA related disease penetrance. (medscape.com)

Although biochemical functions of the human PORCN gene are not well characterized, Wnt signaling may be involved in the phenotypic expression of focal dermal hypoplasia where defective/deficient Wnt signaling could affect cell fate or result in failure of a progenitor cell line to expand. (medscape.com)
Embryos lacking maternal lilli expression show specific defects in the establishment of a functional cytoskeleton during cellularization, and exhibit a pair-rule segmentation phenotype. (sdbonline.org)

Germline MutY human homologue mutations and colorectal cancer: A multisite case-control study. (msdmanuals.com)

Giles, G. G. Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype . (cancervic.org.au)

Studies indicate that focal dermal hypoplasia (FDH) is usually caused by mutations of the PORCN gene, mapped to locus Xp11.23. (medscape.com)

Somatic and germline mutations may occur. (medscape.com)

Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. (jax.org)

Subsequently, 30 index SDHA mutation carriers and 56 nonindex carriers were studied. (medscape.com)
The median age at diagnosis was 43 years (range, 17 to 81 years) in index SDHA mutation carriers compared with 52 years (range, 7 to 90 years) in nonmutation carriers (P = 0.002). (medscape.com)
The estimated penetrance of any SDHA-related manifestation was 10% at age 70 years (95% confidence interval, 0% to 21%) in nonindex mutation carriers. (medscape.com)

Many mutations have been identified in each of the species studied. (creation.com)
Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. (elifesciences.org)

5 This explains why heritable loss-of-function mutations sometimes have pleiotropic effects, not only resulting in white color patterns, but also anemia and/or infertility. (creation.com)
Activating (gain-of-function) mutations, which are generally somatic and not heritable, have been associated with progression in certain cancers. (creation.com)

Point mutations in the WT1 gene result in loss of its regulatory function, with the consequent abnormalities in glomerular formation and gonadal differentiation seen in Denys-Drash syndrome. (medscape.com)
Mutations also result in interesting variety including white animals and white spotting phenotypes. (creation.com)
Through statistics, it is suspected that one-half of cases are inherited, and one-half are the result of new, de novo mutations . (wikidoc.org)

The lesions generally follow the lines of Blaschko and can be a few millimeters to several centimeters in width. (medscape.com)
Photograph shows characteristic linear, erythematous, raised and depressed macules that follow the lines of Blaschko. (medscape.com)
Characteristic lesions that follow the lines of Blaschko. (medscape.com)
Hyperpigmentation that follows the lines of Blaschko on the upper extremity. (medscape.com)
These lesions have been described to develop progressively during adolescence and do not follow the lines of Blaschko. (medscape.com)

The effects of these mutations unexpectedly suggested that pairs of chromosomes might be interacting to control the activity of this gene. (elifesciences.org)
Point mutations may have only minor effects. (wikidoc.org)

The exact origin of the folliculin mutation remains under investigation. (medscape.com)

6 Fourth, none of the studies examined potential confounding factors (such as type of treatment centre and constitutional NF2 mutation type) that can affect age at onset, age at diagnosis, or mortality. (bmj.com)

Subsequent mutation analysis will lead to a definitive diagnosis of the underlying disorder. (bmj.com)
For univariate analyses, the two tailed t test was used for age variables, the χ 2 test for discrete variables (for example, distribution of mutation types), and life tables for mortality analysis. (bmj.com)

4 It encodes a receptor tyrosine kinase involved in the development and homeostasis of several cell lines including melanocytic (pigment), hematologic (blood), mast, and germ cells. (creation.com)
A derived MNTI cell line was sensitive to inhibitors of lysine demethylase, but not to compounds targeting other epigenetic regulators. (ox.ac.uk)

Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. (biomedcentral.com)
Despite these discoveries, the patterns, rates, and properties of cxSVs have primarily been the focus of cancer genomics and such rearrangements remain largely underappreciated in the human germline. (biomedcentral.com)
LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification. (lu.se)

We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. (biomedcentral.com)

Mutations in the Schwannomin-gene are thought to alter the movement and shape of affected cells with loss of contact inhibition. (wikidoc.org)

Anatomy33

Organisms19

Diseases15

Chemicals and Drugs47

Analytical, Diagnostic and Therapeutic Techniques and Equipment33

Psychiatry and Psychology1

Phenomena and Processes117

Disciplines and Occupations1

Information Science4

Health Care4

Genes14

Frameshift6

Genotype3

Polyposis6

Somatic mutations1

Missense mutations1

Nonsense1

Homozygous3

Correlation1

SMAD42

Genetic8

Humans1

Variants2

Chromosome5

Tumor5

Disrupt2

BRCA11

Embryonic2

Patients9

Heterozygous1

Dominant1

Clinical6

Expression2

Homologue1

Colorectal1

Locus1

Occur1

Thyroid1

Carriers3

Species2

Heritable2

Result3

Blaschko5

Effects2

Origin1

Type1

Analysis2

Cell2

Human3

Multiple1

Loss1