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Background <p>Nonsyndromic hearing loss (NSHL) is the major contributor of hereditary hearing loss and inherited mainly as autosomal recessive disease. Early detection of NSHL is highly challenging due to lack of consensus on genetic and mutational background across phenotypes and ethnicities. Emerging evidences indicate involvement of the large structural aberrations such as copy number variations (CNVs) in development of NSHL. The study investigates whether large scale structural genetic variants can contribute to NSHL risk in a genetically stratified ethnicity.</p> Methods and Results <p>A genome-wide genotyping study of 127 NSHL patients was conducted in a Malayalam-speaking Dravidian population to identify the enrichment of CNVs and copy number variation regions (CNVRs) in NSHL and identifying the pathological significance of critical structural variants in NSHL risk. The study identified 225 unique CNVs that were exclusively present in patients of which medium (0.1&#xa0;Mb -1&#xa0;Mb) to large sized deletions (&gt; 1&#xa0;Mb) were more common in patients. The CNVRs in chromosome 14 with no overlapping protein coding genes and chromosome 19 with <i>GRIN3B</i>,<i> TMEM259</i> and <i>WDR18</i> overlapping genes, were significantly enriched in NSHL patients. Among the total number of CNVs that were enriched in NSHL cases, several known overlapping NSHL genes <i>COL11A1</i>,<i> EPS8L2</i>,<i> NARS2</i>,<i> ESRRB</i>,<i> OSBPL2</i>,<i> DSPP</i> were identified. Functional analysis of CNVs revealed novel genes with auditory functions.</p> Conclusions <p>The study unlocks the avenues for wider role of structural variants in the development of NSHL. The CNVs overlapped with novel genes associated to NSHL with potential role in auditory functions and alteration in these genes expression results in hearing impairment.</p>

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Spectrum of Structural Variations in Non-Syndromic Hearing Loss in an Indian Population

  • 期刊论文

  • 发表日期：

    2026年1月12日

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  • Ardra M.,
  • Sindura K.P.,
  • Davis P.,
  • Padmaja M.,
  • Moinak Banerjee

摘要

Background

Nonsyndromic hearing loss (NSHL) is the major contributor of hereditary hearing loss and inherited mainly as autosomal recessive disease. Early detection of NSHL is highly challenging due to lack of consensus on genetic and mutational background across phenotypes and ethnicities. Emerging evidences indicate involvement of the large structural aberrations such as copy number variations (CNVs) in development of NSHL. The study investigates whether large scale structural genetic variants can contribute to NSHL risk in a genetically stratified ethnicity.

Methods and Results

A genome-wide genotyping study of 127 NSHL patients was conducted in a Malayalam-speaking Dravidian population to identify the enrichment of CNVs and copy number variation regions (CNVRs) in NSHL and identifying the pathological significance of critical structural variants in NSHL risk. The study identified 225 unique CNVs that were exclusively present in patients of which medium (0.1 Mb -1 Mb) to large sized deletions (> 1 Mb) were more common in patients. The CNVRs in chromosome 14 with no overlapping protein coding genes and chromosome 19 with GRIN3B, TMEM259 and WDR18 overlapping genes, were significantly enriched in NSHL patients. Among the total number of CNVs that were enriched in NSHL cases, several known overlapping NSHL genes COL11A1, EPS8L2, NARS2, ESRRB, OSBPL2, DSPP were identified. Functional analysis of CNVs revealed novel genes with auditory functions.

Conclusions

The study unlocks the avenues for wider role of structural variants in the development of NSHL. The CNVs overlapped with novel genes associated to NSHL with potential role in auditory functions and alteration in these genes expression results in hearing impairment.