Heterozygous haploinsufficiency. Medical search. Frequent questions

Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type phenotype. (wikipedia.org)
Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product (often a protein). (wikipedia.org)
clarification needed] In the alternative case of haplosufficiency, the loss-of-function allele behaves as above, but the single standard allele in the heterozygous genotype produces sufficient gene product to produce the same, standard phenotype as seen in the homozygote. (wikipedia.org)
A variation of haploinsufficiency exists for mutations in the gene PRPF31, a known cause of autosomal dominant retinitis pigmentosa. (wikipedia.org)
Five heterozygous, nonsynonymous mutations (which cause an amino acid change in the corresponding protein) were identified in TERT, the gene for the telomerase reverse transcriptase catalytic enzyme, among seven unrelated patients. (nih.gov)
Heterozygous mutations in the TERT gene impair telomerase activity by haploinsufficiency and may be risk factors for marrow failure. (nih.gov)
Haploinsufficiency of this gene is hypothesised to be potentially involved in the sleep disturbances seen in these patients. (bmj.com)
We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF -altered endometrial carcinoma. (preprints.org)
Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene. (ox.ac.uk)

This heterozygous genotype may result in a non- or sub-standard, deleterious, and (or) disease phenotype. (wikipedia.org)
Haplosufficiency accounts for the typical dominance of the "standard" allele over variant alleles, where the phenotypic identity of genotypes heterozygous and homozygous for the allele defines it as dominant, versus a variant phenotype produced only by the genotype homozygous for the alternative allele, which defines it as recessive. (wikipedia.org)
When this situation engenders a dominant phenotype we speak of haploinsufficiency (HI). (biomedcentral.com)

An example of this is seen in the case of Williams syndrome, a neurodevelopmental disorder caused by the haploinsufficiency of genes at 7q11.23. (wikipedia.org)
The haploinsufficiency is caused by the copy-number variation (CNV) of 28 genes led by the deletion of ~1.6 Mb. (wikipedia.org)
Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
Why heterozygous mutations in some genes cause disease while others do not? (sirop.org)

In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. (huji.ac.il)

Another example is the haploinsufficiency of telomerase reverse transcriptase which leads to anticipation in autosomal dominant dyskeratosis congenita. (wikipedia.org)
The results of coexpression of wild-type TERT and TERT with aplastic anemia-associated mutations in a telomerase-deficient cell line suggested that haploinsufficiency was the mechanism of telomere shortening due to TERT mutations. (nih.gov)

Results Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. (bmj.com)
We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. (bcm.edu)

Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. (bmj.com)

In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. (aacrjournals.org)
In the last few years, mounting evidence suggests that heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways plays a role in genomic instability and carcinogenesis. (aacrjournals.org)

There were 7 Glycine missense and 6 splice-site variants but no variant leading to haploinsufficiency. (biomedcentral.com)

To investigate a potential correlation of COPS3 haploinsufficiency and disturbed melatonin excretion, we performed fluorescence in situ hybridisation (FISH) using two BACs containing coding exons of COPS3 . (bmj.com)

Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. (bmj.com)
Our bioinformatic analysis, in-depth clinical and genetic workup, and functional studies established haploinsufficiency of UCHL1 as a novel disease mechanism in spastic ataxia. (cegat.com)
2022. Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder . (cardiff.ac.uk)
Newborn Genetic Screening Revealed Increased Levels of Biochemical Indicators in Carriers of Heterozygous Variants. (cdc.gov)

In this thesis I investigated, in cell culture and in animal model, the molecular mechanisms of Foxg1 action and the pathophysiological consequences of Foxg1 haploinsufficiency. (sns.it)

Recently, we showed excessive aggression and altered serotonin brain metabolism in heterozygous Tph2-deficient male mice (Tph2+/-) after predator stress exposure. (ox.ac.uk)

There are 300 known diseases that arise from haploinsufficiency (i.e. heterozygous mutations). (sirop.org)

Haploinsufficiency is the standard explanation for dominant deleterious alleles. (wikipedia.org)
Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. (bcm.edu)

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity. (bcm.edu)

Tph2 haploinsufficiency in animals reflects allelic variation of Tph2 facilitating the elucidation of respective GxE mechanisms. (ox.ac.uk)

In an animal model, I investigated the functional result of Foxg1 haploinsufficiency in mouse visual system. (sns.it)

While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. (preprints.org)
We examined the consequences of CTCF depletion in immortalised human and mouse cells using shRNA knockdown and CRISPR/Cas9 genome editing and examined the growth and development of heterozygous Ctcf ( Ctcf +/- ) mice. (preprints.org)

It is also known that Foxg1 haploinsufficiency in mice results in subtle cortical defects. (sns.it)
In this study, we investigated heterozygous UCHL1 variants on the basis of results from cohort-based burden analyses. (cegat.com)

Here, we undertook a cross-sectional analysis of GABAergic function in deep layer pyramidal neurons of the medial PFC of wild-type and haploinsufficient heterozygous reeler mice. (frontiersin.org)

In this project, we aim to investigate the extent to which dosage compensation occurs in respond to heterozygous mutations in mammalian systems using high throughput CRISPR screens coupled to single cell RNA sequencing. (sirop.org)
FOXI3 haploinsufficiency contributes to low T-cell receptor excision circles and T-cell lymphopenia. (cdc.gov)

Although combined Notch3 heterozygosity in Ins2Akita diabetic animals did not show further deficits, the trypsin digest method revealed that Notch3 haploinsufficiency increased the formation of acellular capillaries in diabetic mice. (utmb.edu)

We identified a total of 34 cases from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). (cegat.com)

A variation of haploinsufficiency exists for mutations in the gene PRPF31, a known cause of autosomal dominant retinitis pigmentosa. (wikipedia.org)
Her most recent efforts have involved studies of CTLA4 deficiency, PIK3CD gain-of-function (GOF), NF-kB2 GOF, IKZF1/IKAROS haploinsufficiency and dominant negative mutations in patients with primary immunodeficiency diseases. (nih.gov)
Loss of B Cells in Patients with Heterozygous Mutations in IKAROS. (nih.gov)
Haploinsufficiency of CTLA-4 due to Heterozygous Germline Mutations Causes Human Immune Dysregulation. (nih.gov)
Heterozygous mutations within the chromodomain helicase DNA binding protein 7 (CHD7) were reported in every two of three CHARGE patients. (nih.gov)
That is why the haploinsufficiency of CHD7 gene due to heterozygous mutations results in not only the postnatal but also the prenatal developmental regulation errors. (nih.gov)
After almost 20 years of characterization of patients with disseminated mycobacterial infections who had monocytopenia, B cell and NK (natural killer) cell cytopenia, Steve Holland's group found heterozygous mutations in the same transcription factor, GATA2, accounting for their disease. (nih.gov)
However, in humans these heterozygous mutations cause haploinsufficiency and underlie myelodysplasia, myeloid leukemia, pulmonary alveolar proteinosis, classical NK cell deficiency, and lymphedema. (nih.gov)
We identified heterozygous mutations in regulator of telomere elongation helicase 1 ( RTEL1 ) in four families. (ersjournals.com)
The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, and were predicted by structural analyses to severely affect the function and/or stability of RTEL1. (ersjournals.com)
Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby, extend the clinical spectrum of RTEL1 deficiency. (ersjournals.com)
To define the clinical features in SHOX haploinsufficiency, however, it is necessary to identify patients with intragenic SHOX mutations or microdeletions involving SHOX as the sole impaired disease gene. (bmj.com)
Background: Aniridia can be caused by isolated PAX6 haploinsufficiency (+/-) due to mutations or heterozygous deletion as part of WAGR/11p deletion syndrome. (nih.gov)
Is haploinsufficiency a sufficient mechanism for MYBPC3 truncating mutations? (rupress.org)
Similar to HCM-causing truncation mutations, CRISPR-mediated cMyBP-C ablation in iPSC-derived human engineered cardiac tissue constructs causes cMyBP-C haploinsufficiency in the heterozygous state. (rupress.org)
A large portion of homozygous lethal mutations also are expected to have viable heterozygous phenotypes. (nih.gov)
Master thesis or technician position: High-throughput investigation of dosage compensation to heterozygous mutations in mammalian systems. (sirop.org)
There are 300 known diseases that arise from haploinsufficiency (i.e. heterozygous mutations). (sirop.org)
Why heterozygous mutations in some genes cause disease while others do not? (sirop.org)
In this project, we aim to investigate the extent to which dosage compensation occurs in respond to heterozygous mutations in mammalian systems using high throughput CRISPR screens coupled to single cell RNA sequencing. (sirop.org)
Disease severity in patients with heterozygous and homozygous mutations largely overlap however, hampering genotype-phenotype correlations. (scientificarchives.com)
We estimate that approximately one-third of individuals with classical EDS have mutations of COL5A1 that result in haploinsufficiency. (qxmd.com)
Seven patients showed clinical pictures of Best vitelliform macular dystrophy (BVMD) and harbored heterozygous mutations compatible with autosomal dominant inheritance. (molvis.org)
Compound heterozygous mutations were detected in four patients who presented a BVMD phenotype, while homozygous mutations were detected in two patients with autosomal recessive bestrophinopathy. (molvis.org)
BVMD, initially described in 1905 by the German ophthalmologist Friedrich Best [ 6 ], is by far the most common disease associated with heterozygous BEST1 mutations. (molvis.org)
While mice heterozygous for loss-of-function Megf8 or Mgrn1 mutations were normal, double heterozygous embryos exhibited an incompletely penetrant syndrome of CHDs with heterotaxy. (stanford.edu)
Heterozygous mutations of human HOXD13, encoding polyalanine expansions or frameshifts, are believed to act by dominant negative or haploinsufficiency mechanisms and are predominantly associated with synpolydactyly phenotypes. (ox.ac.uk)

Haplosufficiency accounts for the typical dominance of the "standard" allele over variant alleles, where the phenotypic identity of genotypes heterozygous and homozygous for the allele defines it as dominant, versus a variant phenotype produced only by the genotype homozygous for the alternative allele, which defines it as recessive. (wikipedia.org)
In contrast to the zebrafish model, and in agreement with recent data, we found normal brain structure in heterozygous and homozygous mutants. (ox.ac.uk)
This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). (openscience.si)

All of the parents were heterozygous carriers of this mutation. (who.int)

For nearly all heterozygous effects on previously reported POI genes, we ruled out even modest penetrance, with 99.9% (13,699 out of 13,708) of all protein-truncating variants found in reproductively healthy women. (dspace-express.com)
Heterozygous variants in the ATP13A3 gene were recently identified as a new cause of adult-onset PAH. (bmj.com)
Independently, compound heterozygous variants in ATP13A3 were identified in two affected siblings and in an unrelated third family. (bmj.com)

1 Since Xp terminal deletions invariably result in short stature irrespective of the breakpoints 2 and small Yp terminal deletions lead to short stature, 3 it has been suggested that a growth gene resides in the PAR1, and that haploinsufficiency of the growth gene causes short stature as a dominant phenotype. (bmj.com)
SHOX haploinsufficiency is common to sex chromosome aberrations associated with terminal Xp or Yp deletions. (bmj.com)
Central to the study are four patient samples with rare heterozygous intragenic deletions in NRXN1 with severe psychosis disorder. (pacb.com)
Our report links patient-specific, heterozygous intragenic deletions in NRXN1 to isoform dysregulation and impaired neuronal maturation and activity in a human and disease-relevant context," the authors note. (pacb.com)
Heterozygous deletions of this gene were already known to cause SCA15, an adult-onset, slowly-progressive ataxia. (biomedcentral.com)

We demonstrate that heterozygous hAPP-J20 mice have reduced Zbtb20 expression in some AD-relevant brain regions, but not others, and that Zbtb20 levels are higher in hAPP-J20 mice than heterozygous Zbtb20 knock-out ( Zbtb20 +/- ) mice. (eneuro.org)
We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. (biomedcentral.com)

However, recapitulating previously observed genetic interactions, we discovered sex-specific brain volumetric alterations in double heterozygous Kctd13xMvp and Kctd13xLat mice. (ox.ac.uk)

The 4E-BP3 expression is altered in CDC73 heterozygous patients and is a potential marker to predict HRTP2/CDC73 haploinsufficiency in a parathyroid cancer syndrome. (nih.gov)
We have identified haploinsufficiency of the COL5A1 gene that encodes the proalpha1(V) chain of type V collagen in the classical form of the Ehlers-Danlos syndrome (EDS), a heritable connective-tissue disorder that severely alters the collagen-fibrillar structure of the dermis, joints, eyes, and blood vessels. (qxmd.com)

In contrast, haploinsufficiency results in variable gene expression and mild phenotypes that are gender, age and deletion parent-of-origin dependent. (confex.com)
Behavioral phenotypes were assessed in these, heterozygous gene knockout and wild-type control animals using standard protocols, including activity (wheel-running), anxiety (open field), exploratory (place preference & T-maze), socialization (interest, preference & memory: tethered & free interactions) and perseveration (radial maze). (confex.com)

We evaluated one of these loci, KCTD13, by modeling haploinsufficiency and complete knockout in mice. (ox.ac.uk)
mice heterozygous for stxbp1 in gabaergic neurons only, showed impaired viability, 50% died within 2-3 weeks, and the rest showed stronger epileptic activity. (brain-knowledge-engine.org)

Viable heterozygote alleles are likely to be widely represented in human disease because of their haploinsufficiency or dominant phenotypic effects. (nih.gov)
As expected, both Gabrb3-knockdown (KD) and heterozygous knockout (+/-) animals show behavioral differences from wild-type C57Bl/6 animals, with Gabrb3-KD animals exhibiting a phenotypic spectrum intermediate between Gabrb3 +/- and total-knockout (KO) animals. (confex.com)
Phenotypic analyses of sh-mediated Gabrb3 knockdown animals complement studies using knockout and haploinsufficiency models, while avoiding early lethality and parent-of-origin dependent complications. (confex.com)

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. (nih.gov)
By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. (nih.gov)

Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. (brain-knowledge-engine.org)

Haploinsufficiency networks identify targetable patterns of allelic deficiency in low mutation ovarian cancer. (stanford.edu)

28. Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation. (nih.gov)

Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product (often a protein). (wikipedia.org)
In Rr ( heterozygous ) individuals, the R allele masks the presence of the r allele, so these individuals also have round peas. (wikipedia.org)
Eight of 28 probands with classical EDS who were heterozygous for expressed polymorphisms in COL5A1 showed complete or nearly complete loss of expression of one COL5A1 allele. (qxmd.com)
They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. (openscience.si)

Our findings suggest that haploinsufficiency of NOBOX can be well tolerated. (scientificarchives.com)

COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. (qxmd.com)

All patients with proven SHOX haploinsufficiency have low-normal to severe short stature and lack demonstrable non-skeletal Turner features or definitive biochemical abnormalities. (bmj.com)

However, in the physiologic state, Schwann cell loss of heterozygosity is not sufficient for neurofibroma formation and Nf1 haploinsufficiency in at least one additional nonneoplastic lineage is required for tumor progression. (bioseek.eu)

SHOX haploinsufficiency usually results in mesomelic short stature and Turner skeletal features, including Madelung deformity with puberty, in subjects with normal gonadal function. (bmj.com)

In this review, we summarise clinical features and diagnostic and therapeutic implications in SHOX haploinsufficiency and overdosage. (bmj.com)

We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. (prolekarniky.cz)

The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers. (who.int)

Anatomy5

Organisms5

Diseases55

Chemicals and Drugs18

Analytical, Diagnostic and Therapeutic Techniques and Equipment8

Psychiatry and Psychology2

Phenomena and Processes34

Information Science2

Gene9

Phenotype3

Genes4

Deletion1

Telomerase2

Pathogenic2

Recurrent1

Proteins2

Missense1

Fluorescence1

Genetic4

Molecular1

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Arise1

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Intellectual1

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Mutations27

Homozygous3

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Demonstrate that heterozygous2

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Phenotypic3

MED13L2

Underlie1

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