• These mutations result in either a reduction or complete loss of activity. (medscape.com)
  • 8. Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations. (nih.gov)
  • Advances in genome-wide molecular cytogenetics allow identification of novel submicroscopic DNA copy number alterations (aCNAs) and copy-neutral loss of heterozygosity (cnLOH) resulting in homozygosity for known gene mutations in myeloid neoplasms. (biomedcentral.com)
  • Loss of heterozygosity affecting these two chromosomes and mutations in TET2 and EZH2 are indicative of a myelodysplastic syndrome with a poor prognosis. (biomedcentral.com)
  • We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. (nature.com)
  • This disorder results from homozygous or compound heterozygous mutations in the DGUOK gene (2p13). (arizona.edu)
  • We describe the phenotype of a patient with severe growth failure where whole exome sequencing (WES) revealed compound heterozygosity for two mutations in the CTC1 gene.Patient and Methods: The patient, the fourth child of healthy non-consanguineous parents, was born. (eurospe.org)
  • Disease severity in patients with heterozygous and homozygous mutations largely overlap however, hampering genotype-phenotype correlations. (scientificarchives.com)
  • BML mutations thus result in defects in DNA repair and genomic instability in the somatic cells, predisposing the patients to cancer development. (medscape.com)
  • The BLM mutations can be found in compound heterozygous forms, homozygous forms, or as single gene mutation forms. (medscape.com)
  • Activity levels for these transcription factors normally associated with diploid gene dosage are important for normal ocular development, with heterozygosity for null mutations in most of these genes causing anterior segment dysgenesis. (biomedcentral.com)
  • Loss of only a single Ku80 allele in Ku(-/+) heterozygous mice causes accelerated aging in skeletal muscle, although post natal growth is normal. (wikipedia.org)
  • [ 41 ] Although poor metabolizers may be homozygous for one particular defective allele (e.g. (medscape.com)
  • As homozygous genomic regions of PGA-derived cells are not compatible with allele-specific RNA-seq, we developed an RNA-seq-based genotyping strategy allowing identification of informative heterozygous regions. (biomedcentral.com)
  • If the two alleles are the same, the individual is homozygous for that allele. (genome.gov)
  • 15. A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell line delineates the position of a putative tumor suppressor gene. (nih.gov)
  • Loss of one copy of the human ATP2C1 gene, encoding SPCA1 (secretory pathway Ca(2+)-ATPase isoform 1), causes Hailey-Hailey disease, a skin disorder. (nih.gov)
  • Disruption of Shh signaling is linked to birth defects, including holoprosencephaly (HPE), a malformation of the forebrain and face thought to result from complex gene-environment interactions. (nih.gov)
  • Homozygous or compound heterozygosity of the MYMK gene (9q34) is responsible for this condition. (arizona.edu)
  • In contrast, conditions of resistance to other hormones, due to defects in other members of the hormone receptor gene family have been reported. (nih.gov)
  • Thyroid (6) and glucocorticoid (7) resistance are other examples of clinical endocrine conditions that can result from receptor gene defects. (nih.gov)
  • These mice, bearing one copy of the wild-type ER gene and one copy of the inactivated ER gene, were screened by Southern and polymerase chain reaction analyses to ensure heterozygosity. (nih.gov)
  • Loss of chromosome 13q, which includes the retinoblastoma (RB) gene focus, occurs in approximately 30% of higher-grade astrocytic tumours. (sagepub.com)
  • In a study of 87 matched pairs of primary tumors of non-small-cell lung carcinoma and nearby normal lung tissue, 25% of the tumors had loss of heterozygosity at the XRCC5 locus and a similar percentage of tumors had hypermethylation of the promoter region of XRCC5. (wikipedia.org)
  • 9. Homozygous deletions on the short arm of chromosome 9 in ovarian adenocarcinoma cell lines and loss of heterozygosity in sporadic tumors. (nih.gov)
  • Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes Golgi stress, apoptosis, and midgestational death in homozygous embryos and squamous cell tumors in adult heterozygotes. (nih.gov)
  • Background: There are limited data on differences in height, bone mineral density (BMD) and pubertal delay between homozygous and heterozygous carriers of IGFALS defects.Objective and hypotheses: To describe clinical and laboratory features and BMD of homozygous and heterozygous carriers of a novel IGFALS mutation in a large Kurdish family.Method: Index cases were two first degree cousins presenting with short stature, low IGF1, ve. (eurospe.org)
  • Heterozygous individuals have been defined as those who show levels of A, AT intermediate between those of normals and those with homozygous deficiency. (nih.gov)
  • Two-thirds of malignant astrocytomas and glioblastomas have homozygous deletions of the region of chromosome 9p that includes the cyclin-dependent kinase inhibitor 2A (CDKN2A) and CDKN2B genes. (sagepub.com)
  • Anophthalmia is the complete absence of the eye, microphthalmia is a small eye usually defined in terms of corneal diameter or axial length, and coloboma is a segmental ocular defect, most commonly a "keyhole" deficiency in the iris. (bmj.com)
  • Background: Loss-of-function of immunoglobulin superfamily member 1 (IGSF1) results in an X-linked syndrome of central hypothyroidism and macroorchidism, variable prolactin deficiency, GH deficiency, increased fat percentage, and delayed puberty testosterone rise despite normal timing of testicular growth.Methods: We investigated the spatial and temporal expression of IGSF1 at the protein and mRNA levels in fetal, neonatal, and adult Wistar rats, using i. (eurospe.org)
  • Background: Loss-of-function of immunoglobulin superfamily, member 1 (IGSF1) causes an x-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency, and variable partial growth hormone deficiency in childhood. (eurospe.org)
  • Patients with emphysema who are found to have the homozygous deficiency have been observed to include a greater percentage of female patients than is usually ob- served in the general emphysema population. (nih.gov)
  • It is estimated that between 1 and 2 percent of patients with COPD have this homozygous deficiency (78, 216). (nih.gov)
  • 98) studied 7 per- sons with homozygous deficiency. (nih.gov)
  • CYP2D6*4/*4), compound heterozygosity (e.g. (medscape.com)
  • Furthermore, compound heterozygosity for the two NOBOX variants was very likely responsible for the severe POI phenotype in the two sisters, who presented with primary amenorrhea (PA), delayed puberty and hypergonadotropic hypogonadism. (scientificarchives.com)
  • improved the diagnostic sensitivity and specificity within the differential analysis between metastatic adenocarcinoma and malignant mesothelioma, and lack of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. (aabioetica.org)
  • At least for Tutankhamun there is evidence of genetic problems (an accumulation of malformations is evident), but apparently not in Cleopatra's case (there is no convincing evidence of infertility, infant mortality or genetic defects, for example). (blogspot.com)
  • Mouse mutants with homozygous defects in Ku80 experience an early onset of senescence. (wikipedia.org)
  • Aneuploidy is an abnormality in the number of chromosomes in a cell due to loss or duplication. (genome.gov)
  • The hete:ozygotes which they studied showed symptoms of bronchitis and did not present the 151 lower lobe perfusion defects frequently noted in homozygotes, They also found no difference in the number of COPD patients among the heterozygotic and the general population. (nih.gov)
  • Analysis of Mutation and Loss of Heterozygosity by Whole-Exome Sequencing Yields Insights into Pseudomyxoma Peritonei. (cdc.gov)
  • Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. (sdbonline.org)
  • To study the question of the role of alpha-1-antitrypsin heterozygosity in the etiopathogenesis of chronic obstructive pulmonary disease (COPD) and to obviate the difficulties of precise diagnosis, Klasen et al. (coriell.org)
  • ZNF445: a homozygous truncating variant in a patient with Temple syndrome and multilocus imprinting disturbance. (cdc.gov)
  • We performed a SNP array on chromosome 6 in CD34 + purified blasts from 19 patients diagnosed with advanced MDS and 8 patients with other myeloid malignancies to evaluate the presence of loss of heterozygosity (LOH) in HLA and its impact on disease progression. (oncotarget.com)
  • Clinical onset of HH symptoms occurs more frequently in adult men than women, as monthly loss of iron due to menstruation in women slows down accumulation and symptoms usually start to appear after menopause. (medscape.com)
  • In summary, the clinical outcome of patients with advanced MDS might be influenced by HLA allelic loss, wich allows subclonal expansions to evade cytotoxic-T and NK cell attack. (oncotarget.com)
  • Describe the audiometric and clinical aspects of genetic hearing loss. (nih.gov)
  • Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. (ersjournals.com)
  • In family studies, it has been found that almost all the homozygous individuals are symptomatic by the age of 40 and that those who are not usually show alterations in pulmonary function studies. (nih.gov)
  • Several human chemokine receptors have been sons than for those homozygous for the wild classified as such on the basis of similarity of type CCR5 (12,17-19,23). (cdc.gov)
  • Defying our own skepticism, in 1990, we established a collaboration with Oliver Smithies' laboratory at the University of North Carolina in Chapel Hill and launched an attempt to produce a mouse homozygous for disrupted function of the estrogen receptor. (nih.gov)
  • It was distinguished from the better-known hemophilia A and B by its presence in both genders due to its autosomal inheritance, a milder bleeding tendency, and the conclusion that the laboratory defect could be corrected by mixing tests with hemophilia A and B plasma. (silverchair.com)
  • A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. (bmj.com)
  • Severity of hearing loss is graded as shown in Table 1 . (nih.gov)
  • The mouse has been an essential animal model for studies in hearing loss, and advances in mouse genetics, including genome sequence and high density single-nucleotide polymorphism (SNP) maps, provide a suitable system for the study of a complex trait such as NIHL [ 6 ]. (prolekarniky.cz)
  • In 1989, Nicotera et al suggested that the major biochemical defect in persons with Bloom syndrome is chronic overproduction of the superoxide radical anion. (medscape.com)
  • However, it is unclear if these defects are indirectly caused by abnormal centriole structure or copy number, or if instead they represent pleiotropic effects due to the direct participation of centrin in the cell division process. (biomedcentral.com)
  • Hepatosplenomegaly is present early with abnormal liver enzymes, cholestasis, steatosis, and hepatocellular loss followed by cirrhosis with portal hypertension. (arizona.edu)
  • A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. (bmj.com)
  • The absence of Nobox accelerates postnatal oocyte loss and abolishes the transition from primordial to growing follicles in mice. (scientificarchives.com)
  • RT-PCR from homozygous mutant fish confirmed the presence of transcripts with indels in all genes. (cancerindex.org)
  • Candidate genes for isolated CeH include TSHβ, TRH receptor (TRHR) or IGSF1 genes while the combined pituitary hormone deficits (CPHDs) are the consequence of defects in embryonic pituitary transcription factors or in the prokineticin receptor 2 (PROKR2).Patients series: Here we report nine males (M) and 15 fema. (eurospe.org)
  • Ovarian histology of Nobox-/- mice showed at day 0 after birth, the presence of oocytes clustered in germ cell cysts and primordial follicles, while at day 7, only few primordial and primary without secondary follicles and at day 14 complete loss of most. (scientificarchives.com)
  • Mouse strains (C57BL/6J) exhibiting age-related hearing loss (AHL) were shown to be more susceptible to noise than other strains [ 6 ]. (prolekarniky.cz)
  • In these persons, there is a loss of elasticity of the lung parenchyma with high compliance. (coriell.org)
  • Cardiac septal defects are common. (arizona.edu)
  • Noise-induced hearing loss (NIHL) is the most common work-related disease in the world and the second cause of hearing loss. (prolekarniky.cz)
  • Noise-induced hearing loss (NIHL) is a worldwide leading occupational health risk in industrialized countries and is the second most common form of sensorineural hearing impairment, after presbyacusis [ 1 ]. (prolekarniky.cz)
  • According to the Department of Veterans Affairs, hearing loss is the most common disability among U.S. troops in the Middle East. (prolekarniky.cz)
  • The purpose of this overview is to increase the awareness of clinicians regarding the diagnosis, management, and genetic counseling of common causes of genetic hearing loss. (nih.gov)
  • The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. (proteopedia.org)
  • Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process. (biomedcentral.com)
  • A significant genetic contribution to the aetiology of non-syndromal MAC has been suggested by previously observed familial clustering of these defects 2 and successful linkage analysis in a small number of families where these disorders segregate in a Mendelian fashion. (bmj.com)
  • Glaucoma is a leading cause of blindness that involves loss of retinal ganglion cells and degeneration of the optic nerve [ 1 ]. (biomedcentral.com)
  • He reported two major personnel losses, one being the departure of Mr. Charles Leasure, Associate Director for Management, to a similar position in the National Human Genome Research Institute, and the other being the departure of Dr. Gerald Poje, Director of NIEHS International Programs and the Environmental Justice initiative, to a presidential appointment on the Chemical Safety Commission. (nih.gov)
  • The sequencing of DNA pools from individual lines is also effective for detecting selective sweeps, because heterozygosity can be calculated in sliding windows from sequences drawn from a pool of haplotypes. (nature.com)
  • Inform the genetic counseling of an individual with genetic hearing loss and their family members. (nih.gov)
  • This heterozygosity is a good thing, evolutionarily, because there is then genetic diversity within that person. (blogspot.com)
  • 5. Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition. (nih.gov)
  • The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity. (biomedcentral.com)
  • A major difficulty is the lack of a precise definition of heterozygosity. (nih.gov)
  • Explain the evaluation strategy to identify the genetic cause of hearing loss in a proband. (nih.gov)
  • Several lines of evidence indicate that Scylla and Charybdis feed into the Inr pathway downstream of PKB: (1) Scylla antagonizes PKB/PDK1-induced overgrowth in the eye, but in vitro kinase assays demonstrate that Scylla and Charybdis do not reduce PKB kinase activity, nor does the loss of Scylla enhance PKB kinase activity. (sdbonline.org)