11/25/2023 0 Comments Type 2a usher syndrome![]() ![]() WES analysis was performed on the proband M567 gDNA (I:1) (Genmed, Inc). Whole exome sequencing (WES) and bioinformatics analysis In the present study, we identified a rare homozygous frameshift mutation in the gene USH2A that originated from maternal UPD by whole exome sequencing (WES) and homozygosity mapping in a Chinese pedigree with Usher syndrome.Ģ.2. The causality and genetic mechanism of Usher syndrome type IIA have not been well documented. The relationship between the variants in the Usher syndrome‐associated genes and the resultant Usher syndrome phenotypes in the patients is highly variable. Detecting UPD is a practical diagnostic approach for rare Mendelian disorders and imprinting disorders caused by homozygosity. 6, 7 Euploidy can result from aneuploid gametes if monosomic rescue, trisomic rescue or gametic complementational restore of normal ploidy occur during early human development. 5 Uniparental disomy (UPD) is the inheritance of both copies of one chromosome from only one parent, without the inheritance of a representative copy from the other parent. Homozygosity has long been known to be related to rare often devastating Mendelian disorders and imprinting diseases. 4 The protein is localized in the basement membrane and has a vital role for development and homeostasis in the inner ear and retina. 3 This gene maps to the chromosome 1q41 and encodes a protein containing 5202 amino acids that contain a pentaxin motif, laminin EGF motifs and numerous fibronectin type III domains. Usher syndrome type IIA (USH2A locus, OMIM 276901) is caused by mutations of the USH2A gene (OMIM 608400). 1, 2 Usher syndrome type II includes USH2A, USH2C and USH2D. Diseases under the umbrella term Usher syndrome include Usher syndrome type I, II and III. Usher syndrome consists of a group of genetically and clinically heterogeneous autosomal recessive disorders with sensorineural hearing deficiencies and progressive retinitis pigmentosa (RP). In summary, our discoveries can help further the understanding of the molecular pathogenesis of Usher syndrome type IIA to advance the prevention, diagnosis and therapy for this disorder. To test potential patients, WES, combined with STR analysis and homozygosity mapping, provides an accurate and useful strategy for genetic diagnosis. Although USH2A is an autosomal recessive disease, the effects of UPD should be informed in genetic counselling since the recurrence risk of an affected child is greatly reduced when the disease is due to the UPD mechanism. The variant was not included in the 1000 Human Genomes Project database, ExAC database, HGMD or gnomAD database, but was included in the ClinVar databases as pathogenic. The p.Arg34Serfs*41 variant produced a predicted truncated protein that removes all functional domains of USH2A. Further homozygosity mapping and STR analysis identified an unusual homozygous variant of proband that originated from maternal uniparental disomy (UPD). We identified a homozygous frameshift variant c.99_100insT (p.Arg34Serfs*41) in the USH2A gene in the proband that showed discordant segregation in the father. Functional domains of the pathogenic variant for USH2A were analysed. Whole exome sequencing (WES), Sanger sequencing, homozygosity mapping, short tandem repeat (STR) analysis and segregation analysis were performed. In the present study, a Chinese family with Usher syndrome was recruited. The mechanisms underlying the Usher syndrome are highly variable. Usher syndrome encompasses a group of genetically and clinically heterogeneous autosomal recessive disorders with hearing deficiencies and retinitis pigmentosa. ![]()
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