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Objective <p>Wolfram syndrome (WS) is a genetically disorder that affect on many organs, and neurodegenerative disorder. Although various clinical dysfunctions may have different onset times, they can collectively contribute to delays in the diagnosis of the disorder. To date, more than 200 pathogenic and likely pathogenic variant have been identified. In the present investigation, we evaluated three families with WS and reported a mutation in the <i>WFS1</i>.</p> Methods <p>This study, we have evaluated mutation in the <i>WFS</i> gene in three consanguineous families including three patients with a history of young-onset DM, progressive hearing loss and optic atrophy further neurological abnormalities.</p> Results <p>Sequencing results showed a novel homozygous stop-gain variant, c.1444A &gt; T (p.K482X), and two previously reported mutations (c.2006A &gt; G and c.2105G &gt; A) in exon 8 of <i>WFS1</i> gene. The variant interpretation was done according to the genetic guidelines. Finally, p.K482X was determined as a novel pathogen variant. Also, analysis showed that variants in parents were heterozygous.</p> Conclusions <p>The present survey, revealed a novel nonsense mutation in the wolframin protein, creates a frameshift which causes a premature stop codon truncating the protein in amino acid 482 residues. This mutation occurs in transmembrane domain and causes elimination of 46% of wolframin protein.</p>

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Evaluation of pathogenic variant in WFS1 in a patient with Wolfram syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月17日

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  • Marziyeh Hoseinzadeh,
  • Mohammad Mehdi Jahani,
  • Samane Nasrniya,
  • Mohammad Amin Tabatabaiefar

摘要

Objective

Wolfram syndrome (WS) is a genetically disorder that affect on many organs, and neurodegenerative disorder. Although various clinical dysfunctions may have different onset times, they can collectively contribute to delays in the diagnosis of the disorder. To date, more than 200 pathogenic and likely pathogenic variant have been identified. In the present investigation, we evaluated three families with WS and reported a mutation in the WFS1.

Methods

This study, we have evaluated mutation in the WFS gene in three consanguineous families including three patients with a history of young-onset DM, progressive hearing loss and optic atrophy further neurological abnormalities.

Results

Sequencing results showed a novel homozygous stop-gain variant, c.1444A > T (p.K482X), and two previously reported mutations (c.2006A > G and c.2105G > A) in exon 8 of WFS1 gene. The variant interpretation was done according to the genetic guidelines. Finally, p.K482X was determined as a novel pathogen variant. Also, analysis showed that variants in parents were heterozygous.

Conclusions

The present survey, revealed a novel nonsense mutation in the wolframin protein, creates a frameshift which causes a premature stop codon truncating the protein in amino acid 482 residues. This mutation occurs in transmembrane domain and causes elimination of 46% of wolframin protein.