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<p>We report a family affected with childhood onset distal muscle weakness with a heterozygous chromosome 9q34 deletion encompassing the <i>SPTAN1</i> gene. The deletion was detected through exome-sequencing based copy number variant (CNV) detection, segregates in four patients and is non-penetrant in two other relatives. Electromyography, muscle MRI and muscle biopsy revealed a myopathic disease phenotype. Cellular consequences of the deletion were investigated using qPCR and western blotting on patient-derived fibroblasts, which revealed a reduction of RNA but not protein levels. Immunocytochemistry was performed on muscle tissue which did not reveal reduction of α-II-spectrin. <i>SPTAN1</i> loss-of-function variants have previously been reported to cause distal hereditary motor neuropathy and recently distal myopathy. Here, we confirm the role of <i>SPTAN1</i> haploinsufficiency as a cause of distal myopathy. We propose an age-dependent lack of α-II-spectrin and suggest CNV detection in repurposed exome sequencing as an important diagnostic tool.</p>

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A heterozygous 9q34 deletion encompassing SPTAN1 as a cause of distal myopathy

  • 期刊论文

  • 发表日期：

    2025年9月25日

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  • Liedewei Van de Vondel,
  • Jonathan De Winter,
  • Alice Monticelli,
  • Natacha Camacho,
  • Tine Deconinck,
  • Katrien Janssens,
  • Goedele Malfroid,
  • Alicia Alonso-Jiménez,
  • German Demidov,
  • Steven Laurie,
  • Willem De Ridder,
  • Biljana Ermanoska,
  • Vincent Timmerman,
  • Jonathan Baets

摘要

We report a family affected with childhood onset distal muscle weakness with a heterozygous chromosome 9q34 deletion encompassing the SPTAN1 gene. The deletion was detected through exome-sequencing based copy number variant (CNV) detection, segregates in four patients and is non-penetrant in two other relatives. Electromyography, muscle MRI and muscle biopsy revealed a myopathic disease phenotype. Cellular consequences of the deletion were investigated using qPCR and western blotting on patient-derived fibroblasts, which revealed a reduction of RNA but not protein levels. Immunocytochemistry was performed on muscle tissue which did not reveal reduction of α-II-spectrin. SPTAN1 loss-of-function variants have previously been reported to cause distal hereditary motor neuropathy and recently distal myopathy. Here, we confirm the role of SPTAN1 haploinsufficiency as a cause of distal myopathy. We propose an age-dependent lack of α-II-spectrin and suggest CNV detection in repurposed exome sequencing as an important diagnostic tool.