Key result
Next-generation sequencing combined with muscle MRI identified a novel heterozygous mutation in the MYH7 gene (p.Ser1435Pro) as the cause of autosomal dominant distal myopathy in a family previously misdiagnosed with a RYR1 mutation.
Case Report (n=5)
Combining next-generation sequencing data with muscle MRI patterns is crucial for accurate molecular diagnosis in inherited muscle disorders.
May prompt re-evaluation of RYR1 diagnoses in distal myopathy; extends MYH7 spectrum but remains hypothesis-generating pending larger studies.
BACKGROUND: Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family. CASE PRESENTATION: The proposita, being found to harbor a novel heterozygous mutation in the RYR1 gene (p.Glu294Lys), was initially diagnosed with core myopathy. Subsequently, consideration of muscle magnetic resonance imaging (MRI) features and extension of family study led this diagnosis to be questioned. Use of next-generation sequencing analysis identified a novel mutation in the MYH7gene (p.Ser1435Pro) that segregated in the affected family members. CONCLUSIONS: This study identified a novel mutation in MYH7 in a family where the conclusive molecular diagnosis was reached through a complicated path. This case report might raise awareness, among clinicians, of the need to interpret NGS data in combination with muscle MRI patterns so as to facilitate the pinpointing of the main molecular etiology in inherited muscle disorders.
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Astrea et al. (2016) conducted a case report in Autosomal dominant distal myopathy (n=5). Next-generation sequencing and muscle MRI vs. Traditional Sanger sequencing was evaluated on Identification of the causative genetic mutation. Next-generation sequencing combined with muscle MRI identified a novel heterozygous mutation in the MYH7 gene (p.Ser1435Pro) as the cause of autosomal dominant distal myopathy in a family previously misdiagnosed with a RYR1 mutation.
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