![]() Syndrome-causative genes and the resultant Usher syndrome The association between the variants in the Usher Mutations among patients with Usher syndrome type IIA. Eudy et al ( 5) was the first to identify USH2A Syndrome type IIA and non-syndromic RP ( 13). USH2A gene have been identified in patients with Usher Vital role in the development and homeostasis of the inner ear and The protein is localized in the basement membrane and serves a Laminin epidermal growth factor (EGF) motifs and numerousįibronectin type III domains ( 10). This gene maps to chromosome 1q41, encoding a proteinĥ,202 amino acids in length that is comprised of a pentaxin motif, Protein, Usher Syndrome Type IIa Protein, DJ1111A8.1 and Usherin, USH2, US2, Usher Syndrome 2A, Usher Syndrome Type-2A Pedigree which had been previously mapped to the USH2B locus ofĬhromosome 3p23-p24.2, the designation for the USH2B locus was Result of mutations of the ADGRV1 gene (OMIM, 602851)ĪDGRV1 and PDZD7 genes (OMIM, 612971) ( 7) and USH2D (OMIM, 611383) can be causedīy mutations of the whirlin ( WHRN) gene (OMIM, 607928)Īdhesion G-protein coupled receptor V1 gene in an Usher II syndrome Of mutations of the USH2A gene (OMIM, 608400) ( 5), whereas USH2C (OMIM, 605472) is the Usher syndrome type IIA (USH2A locus) (OMIM, 276901) is the result Is genetically heterogeneous, including USH2A, USH2C and USH2D. Responses, and type II is the most common type amongst the three (USH2) present with mild hearing impairments but normal vestibular Progressive retinitis pigmentosa (RP) and sensorineural hearingĭeficiencies, including Usher syndrome types I, II and III ![]() Usher syndrome is a group of genetically andĬlinically heterogeneous autosomal recessive diseases with ![]() The present discovery may assist in understanding the molecular pathogenesis underlying the development of RP and Usher syndrome type IIA, and in the development of diagnostic, therapeutic and genetic counseling strategies in patients with Usher syndrome type IIA disease. To the best of our knowledge, the present study is the first to identify two novel pathogenic variants, c.T449G (p.L150*) and c.T10695A (p.Y3565*), in the USH2A gene in a patient with Usher syndrome type IIA, thereby expanding the known spectrums of USH2A causative mutations. Additionally, the protein structure was shown to be highly conserved by comparing Homo sapiens USH2A to eight other species. It was shown that Ush2a mRNA expression levels were higher in the retina compared with those in the eye tissues (lens, sclera and cornea), uterus, ovary, breast, testis, spleen, kidney, liver, intestine, brain, skeletal muscle and blood. The p.L150* variant was predicted to produce a truncated protein which lacked almost all the functional domains of USH2A, whereas the p.Y3565* variant is located in one of the fibronectin type 3 domains, resulting in the loss of several fibronectin type 3 domains at the C‑terminus of USH2A by producing the truncated protein. Novel nonsense compound heterozygous variants, c.T449G (p.L150*) and c.T10695A (p.Y3565*), were identified in the USH2A gene, which showed co‑segregation with the disease phenotype causing Usher syndrome type IIA in the recruited Chinese pedigree. The expression profiles and functional effects of the pathogenic variants of USH2A identified were analyzed. In the present study, a Chinese family with Usher syndrome was recruited, and targeted next‑generation sequencing, Sanger sequencing and segregation analysis were performed. The association between Usher syndrome‑causative genes and resultant Usher syndrome phenotypes in patients are highly variable. Usher syndrome refers to a group of genetically and clinically heterogeneous autosomal recessive diseases with retinitis pigmentosa (RP) and hearing deficiencies.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |