Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct

Genetic hearing loss is a common sensory disorder, and its cause is highly heterogeneous. In this study, by targeted next-generation sequencing of 414 known deafness genes, we identified compound heterozygous mutations p.R34X/p.M413T in TMC1 and p.S3417del/p.R1407T in MYO15A in two recessive Chinese Han deaf families. Intrafamilial cosegregation of the mutations with the hearing phenotype was confirmed in both families by the Sanger sequencing. Auditory features of the affected individuals are consistent with that previously reported for recessive mutations in TMC1 and MYO15A. The two novel mutations identified in this study, p.M413T in TMC1 and p.R1407T in MYO15A, are classified as likely pathogenic according to the guidelines of ACMG. Our study expanded the mutation spectrums of TMC1 and MYO15A and illustrated that genotype-phenotype correlation in combination with next-generation sequencing may improve the accuracy for genetic diagnosis of deafness.

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An iPSC line (TYWHSTi002-A) derived from a patient with Pendred syndrome caused by compound heterozygous mutations in the SLC26A4 gene

Stem Cell Research ◽

10.1016/j.scr.2020.101919 ◽

2020 ◽

Vol 47 ◽

pp. 101919

Author(s):

Xinsheng Chen ◽

Yang Yang ◽

Liqiong Luo ◽

Lijuan Xu ◽

Bei Liu ◽

...

Keyword(s):

Compound Heterozygous ◽

Ipsc Line ◽

Pendred Syndrome ◽

Slc26a4 Gene ◽

Compound Heterozygous Mutations

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Targeted Next-Generation Sequencing Identified Compound Heterozygous Mutations in MYO15A as the Probable Cause of Nonsyndromic Deafness in a Chinese Han Family

Neural Plasticity ◽

10.1155/2020/6350479 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Longhao Wang ◽

Lin Zhao ◽

Hu Peng ◽

Jun Xu ◽

Yun Lin ◽

...

Keyword(s):

Hearing Loss ◽

Next Generation Sequencing ◽

Cochlear Implantation ◽

Compound Heterozygous ◽

Next Generation ◽

Chinese Han ◽

Targeted Next Generation Sequencing ◽

Before And After ◽

Compound Heterozygous Mutations ◽

Generation Sequencing

Hearing loss is a highly heterogeneous disorder, with more than 60% of congenital cases caused by genetic factors. This study is aimed at identifying the genetic cause of congenital hearing loss in a Chinese Han family. Auditory evaluation before and after cochlear implantation and targeted next-generation sequencing of 140 deafness-related genes were performed for the deaf proband. Compound heterozygous mutations c.3658_3662del (p. E1221Wfs∗23) and c.6177+1G>T were identified in MYO15A as the only candidate pathogenic mutations cosegregated with the hearing loss in this family. These two variants were absent in 200 normal-hearing Chinese Hans and were classified as likely pathogenic and pathogenic, respectively, based on the ACMG guideline. Our study further expanded the mutation spectrum of MYO15A as the c.3658_3662del mutation is novel and confirmed that deaf patients with recessive MYO15A mutations have a good outcome for cochlear implantation.

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