Dear Editor,Actins are a family of essential cytoskeletal proteins involved in nearly all cellular processes（Lambrechts et al.,2004）.Of the six human genes that encode actins,only ACTG1and ACTB are ubiquitously expr...Dear Editor,Actins are a family of essential cytoskeletal proteins involved in nearly all cellular processes（Lambrechts et al.,2004）.Of the six human genes that encode actins,only ACTG1and ACTB are ubiquitously expressed.ACTG1（OMIM#604717）,which is linked to the DFNA20/26 locus,wasidentified in autosomal dominant, non-syndromic hearing loss （NSHL） cases （Baek et al., 2012; Liu et al., 2008; Park et al., 2013; Yuan et al., 2016）. In addition, some ACTG1 （OMIM #614583） mutations are associated with Baraitser-Winter syndrome, which is characterized by developmental delay, facial dysmorphologies, brain malformations, colobomas, and variable hearing loss （Riviere et al., 2012）.展开更多
Objectives To review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics o...Objectives To review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics on NSHL in China Methods The presented data are based on a review of the literature as well as the author's experience with NSHL and communications with other researchers in China over the past 3 years Results Currently, 23 deafness genes related to NSHL have been cloned and identified Some genes are associated with both NSHL and syndromic hearing loss (SHL), in both dominant and recessive deafness Deafness genes have a highly specific expression pattern in the inner ear Some functional categories are starting to emerge from a characterization of deafness genes There are interacting genes in the genetic background that influence the extent of hearing impairment The GJB3 gene, which is associated with high frequency hearing impairment, was cloned in a Chinese laboratory Mutations in some genes, such as GJB2 and mitochondrial 12S rRNA, have been screened in Chinese patients with NSHL Mapping new deafness gene loci as well as identifying new genes and their functions is an active area of study in China Conclusions It is challenging for us to continue identifying new deafness genes and analyze gene functions By identifying genes responsible for monogenic hearing impairment, more insight may be gained into the molecular process of hearing and the pathology of hearing loss展开更多
Background： Nonsyndrornic hearing loss （NSHL） is highly heterogeneous, in which more than 90 causative genes have currently been identified. DFNA5 is one of the deathess genes that known to cause autosomal dominant...Background： Nonsyndrornic hearing loss （NSHL） is highly heterogeneous, in which more than 90 causative genes have currently been identified. DFNA5 is one of the deathess genes that known to cause autosomal dominant NSHL. Until date, only five DFN.45 mutations have been described in eight families worldwide. In this study, we reported the identification of a novel pathogenic mutation causing DFNA5 deafness in a five-generation Chinese family. Methods： Alter detailed clinical evaluations of this family, the genomic DNA of three affected individuals was selected for targeted exome sequencing of 101 known deafness genes, as well as mitochondrial DNA and microRNA regions. Co-segregation analysis between the hearing loss and the candidate variant was confirmed in available family members by direct polymerase chain reaction （PCR）-Sanger sequencing. Real-time PCR （RT-PCR） was pertormed to investigate the potential effect of the pathogenic mutation on messenger RNA splicing. Results： Clinical evaluations revealed a similar deafness phenotype in this family to that of previously reported DFNA5 families with autosomal dominant, late-onset bearing loss. Molecular analysis identified a novel splice site mutation in DFNA5 intron 8 （IVSS＋ 1 delG）. The mutation segregated with the hearing loss of the family and was absent in 120 unrelated control DNA samples of Chinese origin. RT-PCR showed skipping of exon 8 in the mutant transcript. Conclusions： We identified a novel DFNA5 mutation IVS8＋1 delG in a Chinese family which led to skipping ofexon 8. This is the sixth DFNA5 mutation relates to hearing loss and the second one in DFNA5 intron 8. Our findings provide further support to the hypothesis that the DFNA5-associated hearing loss represents a mechanism of gain-of-function.展开更多
基金supported by the National Natural Science Foundation of China(81530032)the National Key Basic Research Program of China(2014CB943001)
文摘Dear Editor,Actins are a family of essential cytoskeletal proteins involved in nearly all cellular processes（Lambrechts et al.,2004）.Of the six human genes that encode actins,only ACTG1and ACTB are ubiquitously expressed.ACTG1（OMIM#604717）,which is linked to the DFNA20/26 locus,wasidentified in autosomal dominant, non-syndromic hearing loss （NSHL） cases （Baek et al., 2012; Liu et al., 2008; Park et al., 2013; Yuan et al., 2016）. In addition, some ACTG1 （OMIM #614583） mutations are associated with Baraitser-Winter syndrome, which is characterized by developmental delay, facial dysmorphologies, brain malformations, colobomas, and variable hearing loss （Riviere et al., 2012）.
文摘Objectives To review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics on NSHL in China Methods The presented data are based on a review of the literature as well as the author's experience with NSHL and communications with other researchers in China over the past 3 years Results Currently, 23 deafness genes related to NSHL have been cloned and identified Some genes are associated with both NSHL and syndromic hearing loss (SHL), in both dominant and recessive deafness Deafness genes have a highly specific expression pattern in the inner ear Some functional categories are starting to emerge from a characterization of deafness genes There are interacting genes in the genetic background that influence the extent of hearing impairment The GJB3 gene, which is associated with high frequency hearing impairment, was cloned in a Chinese laboratory Mutations in some genes, such as GJB2 and mitochondrial 12S rRNA, have been screened in Chinese patients with NSHL Mapping new deafness gene loci as well as identifying new genes and their functions is an active area of study in China Conclusions It is challenging for us to continue identifying new deafness genes and analyze gene functions By identifying genes responsible for monogenic hearing impairment, more insight may be gained into the molecular process of hearing and the pathology of hearing loss
基金This study was supported by a grant from the Jiangsu Health Administration，by a research grant award from the National Natural Science Foundation of China，by a grant from the Research Special Fund for Public Welfare Industry of Health,Ministry of Health of China
文摘Background： Nonsyndrornic hearing loss （NSHL） is highly heterogeneous, in which more than 90 causative genes have currently been identified. DFNA5 is one of the deathess genes that known to cause autosomal dominant NSHL. Until date, only five DFN.45 mutations have been described in eight families worldwide. In this study, we reported the identification of a novel pathogenic mutation causing DFNA5 deafness in a five-generation Chinese family. Methods： Alter detailed clinical evaluations of this family, the genomic DNA of three affected individuals was selected for targeted exome sequencing of 101 known deafness genes, as well as mitochondrial DNA and microRNA regions. Co-segregation analysis between the hearing loss and the candidate variant was confirmed in available family members by direct polymerase chain reaction （PCR）-Sanger sequencing. Real-time PCR （RT-PCR） was pertormed to investigate the potential effect of the pathogenic mutation on messenger RNA splicing. Results： Clinical evaluations revealed a similar deafness phenotype in this family to that of previously reported DFNA5 families with autosomal dominant, late-onset bearing loss. Molecular analysis identified a novel splice site mutation in DFNA5 intron 8 （IVSS＋ 1 delG）. The mutation segregated with the hearing loss of the family and was absent in 120 unrelated control DNA samples of Chinese origin. RT-PCR showed skipping of exon 8 in the mutant transcript. Conclusions： We identified a novel DFNA5 mutation IVS8＋1 delG in a Chinese family which led to skipping ofexon 8. This is the sixth DFNA5 mutation relates to hearing loss and the second one in DFNA5 intron 8. Our findings provide further support to the hypothesis that the DFNA5-associated hearing loss represents a mechanism of gain-of-function.
