Dataset Information

Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

ABSTRACT:

Background

Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molecular data from 21 Chinese deaf families who did not have hotspot mutations in the common deafness genes GJB2, SLC26A4, GJB3, and MT-RNR1.

Method

Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed in probands of 12 families, while whole-exome sequencing (WES) or trio-WES was used for the remaining nine families.

Results

Potential pathogenic mutations in a total of 12 deafness genes were identified in 13 probands; the mutations were observed in GJB2, CDH23, EDNRB, MYO15A, OTOA, OTOF, TBC1D24, SALL1, TMC1, TWNK, USH1C, and USH1G, with eight of the identified mutations being novel. Further, a copy number variant (CNV) was detected in one proband with heterozygous deletion of chromosome 4p16.3-4p15.32. Thus, the total diagnostic rate using NGS in our deafness patients reached 66.67% (14/21).

Conclusions

These results expand the mutation spectrum of deafness-causing genes and provide support for the use of NGS detection technologies for routine molecular diagnosis in Chinese deaf populations.

SUBMITTER: Xiang YB

PROVIDER: S-EPMC7767562 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

Xiang Yan-Bao YB Xu Chen-Yang CY Xu Yun-Zhi YZ Li Huan-Zheng HZ Zhou Li-Li LL Xu Xue-Qin XQ Chen Zi-Hui ZH Tang Shao-Hua SH

Molecular genetics & genomic medicine 20201023 12

<h4>Background</h4>Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molecular data from 21 Chinese deaf families who did not have hotspot mutations in the common deafness genes GJB2, SLC26A4, GJB3, and MT-RNR1.<h4>Method</h4>Targeted next-genera ...[more]

PMID: 33095980

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Project description:BACKGROUND: Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. OBJECTIVE: To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. DESIGN: DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. RESULTS: Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. CONCLUSION: For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.

Dataset Information

Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

Background

Method

Results

Conclusions

Publications

Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

Similar Datasets

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