Scholarlink

Background <p>Hereditary hearing loss (HHL) is a genetically heterogeneous disorder, with autosomal recessive non-syndromic hearing loss (ARNSHL) comprising a significant proportion of cases globally. To investigate its genetic basis, we performed whole-exome sequencing (WES) in four consanguineous Iranian families affected by ARNSHL.</p> Methods <p>WES was performed for the proband of each family using an Illumina platform. Secondary analysis was conducted with the DRAGEN Bio-IT Platform, and variant annotation was performed using wANNOVAR. Variants were prioritized based on inheritance patterns and bioinformatic predictions. Selected variants were validated by Sanger sequencing and assessed according to American College of Medical Genetics and Genomics / Association for Molecular Pathology (ACMG/AMP) guidelines.</p> Results <p>Through this approach, we identified a previously reported missense variant in <i>CDH23</i>:c.5908G &gt; A (p.Glu1970Lys), a nonsense variant in <i>PDZD7</i>:c.175&#xa0;C &gt; T (p.Arg59Ter) with no prior clinical report, and a recurrent nonsense variant in <i>CDC14A</i>:c.1126&#xa0;C &gt; T (p.Arg376Ter) in two families, providing further support as a founder mutation in Iran.</p> Conclusion <p>These findings illustrate the potential diagnostic value of WES in ARNSHL and report, for the first time, a clinical association of the <i>PDZD7</i> variant (c.175&#xa0;C &gt; T) with hearing loss. Pathogenic variants in <i>CDH23</i> and <i>CDC14A</i> are consistent with their established involvement in HHL. Overall, this study provides additional insights into the genetic landscape and genotype–phenotype correlations in ARNSHL.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

First clinical report of a rare PDZD7 nonsense variant and recurrent mutations in Iranian families with autosomal recessive non-syndromic hearing loss

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

查看全文
  • Hossein Ghasemi,
  • Emran Esmaeilzadeh,
  • Fateme Zahedi Abghari,
  • Marzieh Mohseni,
  • Erfan Akbarpoor,
  • Hamid Reza Khorram Khorshid,
  • Niloofar Bazazzadegan,
  • Reza Najafipour

摘要

Background

Hereditary hearing loss (HHL) is a genetically heterogeneous disorder, with autosomal recessive non-syndromic hearing loss (ARNSHL) comprising a significant proportion of cases globally. To investigate its genetic basis, we performed whole-exome sequencing (WES) in four consanguineous Iranian families affected by ARNSHL.

Methods

WES was performed for the proband of each family using an Illumina platform. Secondary analysis was conducted with the DRAGEN Bio-IT Platform, and variant annotation was performed using wANNOVAR. Variants were prioritized based on inheritance patterns and bioinformatic predictions. Selected variants were validated by Sanger sequencing and assessed according to American College of Medical Genetics and Genomics / Association for Molecular Pathology (ACMG/AMP) guidelines.

Results

Through this approach, we identified a previously reported missense variant in CDH23:c.5908G > A (p.Glu1970Lys), a nonsense variant in PDZD7:c.175 C > T (p.Arg59Ter) with no prior clinical report, and a recurrent nonsense variant in CDC14A:c.1126 C > T (p.Arg376Ter) in two families, providing further support as a founder mutation in Iran.

Conclusion

These findings illustrate the potential diagnostic value of WES in ARNSHL and report, for the first time, a clinical association of the PDZD7 variant (c.175 C > T) with hearing loss. Pathogenic variants in CDH23 and CDC14A are consistent with their established involvement in HHL. Overall, this study provides additional insights into the genetic landscape and genotype–phenotype correlations in ARNSHL.