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Background <p>Mitochondrial disorders, often caused by mutations in mitochondrial or nuclear DNA, disrupt respiratory function and lead to multisystemic symptoms, including neurological, visual, auditory, and musculoskeletal impairments. The Growth Factor, ERV1-like gene (<i>GFER</i>), also known as Augmenter of Liver Regeneration (<i>ALR</i>), plays a critical role in mitochondrial function and oxidative stress response. Mutations in <i>GFER</i> are associated with autosomal recessive mitochondrial disorders characterized by progressive muscular hypotonia, congenital cataracts, and developmental delays.</p> Method <p>This study describes an Iranian family with two siblings presenting congenital cataracts, proximal myopathy, and polyneuropathy.</p> Results <p>Whole exome sequencing identified a homozygous <i>GFER</i> mutation (NM_005262.3:c.581G &gt; A, p.Arg194His), confirmed by Sanger sequencing. Clinical evaluations revealed elevated creatine kinase levels, myopathic changes in muscle biopsies, and electrodiagnostic evidence of motor demyelinating polyneuropathy in the proband. The siblings exhibited mild progressive proximal myopathy without significant disability, differing from previous reports of severe neonatal-onset symptoms. In silico analysis predicted that the p.Arg194His mutation disrupts GFER’s enzymatic activity, impairing oxidative protein folding and mitochondrial function.</p> Conclusion <p>This study highlights the phenotypic variability of <i>GFER</i>-related disorders and provides the first report of pure demyelinating motor polyneuropathy associated with a <i>GFER</i> mutation, underscoring its role in myelin formation and function. These findings contribute to the understanding of GFER’s involvement in mitochondrial and neurodegenerative pathologies, emphasizing the need for further research into its molecular mechanisms and therapeutic potential.</p>

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Myo-Neuropathy and Congenital Bilateral Cataract Due to a GFER Variant in an Iranian Family

  • 期刊论文

  • 发表日期：

    2025年10月8日

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  • Aida Ghasemi,
  • Seyed Jalaleddin Hadei,
  • Zahra Salami,
  • Hiva Saffar,
  • Hossein Najmabadi,
  • Ali Asghar Okhovat

摘要

Background

Mitochondrial disorders, often caused by mutations in mitochondrial or nuclear DNA, disrupt respiratory function and lead to multisystemic symptoms, including neurological, visual, auditory, and musculoskeletal impairments. The Growth Factor, ERV1-like gene (GFER), also known as Augmenter of Liver Regeneration (ALR), plays a critical role in mitochondrial function and oxidative stress response. Mutations in GFER are associated with autosomal recessive mitochondrial disorders characterized by progressive muscular hypotonia, congenital cataracts, and developmental delays.

Method

This study describes an Iranian family with two siblings presenting congenital cataracts, proximal myopathy, and polyneuropathy.

Results

Whole exome sequencing identified a homozygous GFER mutation (NM_005262.3:c.581G > A, p.Arg194His), confirmed by Sanger sequencing. Clinical evaluations revealed elevated creatine kinase levels, myopathic changes in muscle biopsies, and electrodiagnostic evidence of motor demyelinating polyneuropathy in the proband. The siblings exhibited mild progressive proximal myopathy without significant disability, differing from previous reports of severe neonatal-onset symptoms. In silico analysis predicted that the p.Arg194His mutation disrupts GFER’s enzymatic activity, impairing oxidative protein folding and mitochondrial function.

Conclusion

This study highlights the phenotypic variability of GFER-related disorders and provides the first report of pure demyelinating motor polyneuropathy associated with a GFER mutation, underscoring its role in myelin formation and function. These findings contribute to the understanding of GFER’s involvement in mitochondrial and neurodegenerative pathologies, emphasizing the need for further research into its molecular mechanisms and therapeutic potential.