Truncating Variants in the Majority of the Cytoplasmic Domain of Are Unlikely to Cause Usher Syndrome 1F

Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics.
Source: Journal of Molecular Diagnostics - Category: Pathology Authors: Tags: Regular article Source Type: research

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Conclusion.: Our. Results.: provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for...
Source: Clinical and Experimental Otorhinolaryngology - Category: ENT & OMF Tags: Clin Exp Otorhinolaryngol Source Type: research
CONCLUSIONS: Genetic and phenotypic heterogeneity are very common in both isolated and syndromic retinal dystrophies and sensorineural hearing loss. Our findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes. PMID: 31566003 [PubMed - as supplied by publisher]
Source: European Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Eur J Ophthalmol Source Type: research
AbstractPurposeUsher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH).MethodsA total of 268 genetically confirmed USH patients underwent electrophysiological examinations in the context of multimodal ophthalmological examination in the study (75 USH1, 189 USH2 and four USH3). Full-field electroretinography (ERG) was performed accord...
Source: Documenta Ophthalmologica - Category: Opthalmology Source Type: research
Conclusions: Although the sample size is very small, it is tempting to speculate that the gene frequencies in Cuba are distinct from other populations mainly due to an “island effect” and genetic drift. The two recurrent mutations appear to be of Spanish origin. Further studies with a larger cohort are needed to elucidate the real genetic landscape of Usher syndrome in the Cuban population.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
CONCLUSION: Our report emphasizes the advantage of new genetic tests to investigate atypical presentations of known retinal disorders found in syndromic settings. In addition, we speculate that the underlying ciliopathy might possibly aggravate the phenotype of this case of Usher syndrome. PMID: 30991842 [PubMed - as supplied by publisher]
Source: European Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Eur J Ophthalmol Source Type: research
In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in pr...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Authors: Tsang SH, Aycinena ARP, Sharma T Abstract Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking. Because nearly every cell in the body (including the photoreceptors) contains cilia, defects in ciliary proteins typically affect multiple organ systems. Usher syndrome is the most common syndromic cause of retinitis pigmentosa (RP) and accounts for 10-20% of cases of RP Inheritance is autosomal recessive, and the retinal dystrophy is usually rod-cone dystrophy (Figs. 32.1 and 32.2). These patients have RP with sensorineural hearing loss (partial or complete) sinc...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Conclusion: These results promote generalization of early molecular screening for Usher syndrome in deaf children.
Source: Otology and Neurotology - Category: ENT & OMF Tags: BASIC SCIENCE Source Type: research
AbstractMost cases of Usher syndrome type II (USH2) are due to mutations in theUSH2A gene. There are no effective treatments or ideal animal models for this disease, and the pathological mechanisms of USH2 caused byUSH2A mutations are still unknown. Here, we constructed aush2a knockout (ush2a−/−) zebrafish model using TALEN technology to investigate the molecular pathology of USH2. An early onset auditory disorder and abnormal morphology of inner ear stereocilia were identified in theush2a−/− zebrafish. Consequently, the disruption of Ush2a in zebrafish led to a hearing impairment, like that in mamm...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusion: We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation inAdgrv1, the human Usher syndrome 2C gene. The retinal degeneration was cause by a mutation inPde6b, while the hearing loss was caused by a mutation inAdgrv1.Cell Physiol Biochem 2018;47:1883 –1897
Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
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