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Refining NGS diagnosis of muscular disorders
  1. Mathieu Cerino1,2,3,
  2. Emmanuelle Salort-Campana1,4,
  3. Svetlana Gorokhova1,2,
  4. Amandine Sevy4,
  5. Nathalie Bonello-Palot1,2,
  6. Nicolas Levy1,2,5,
  7. Shahram Attarian1,4,
  8. Marc Bartoli1,
  9. Martin Krahn1,2
  1. 1 Aix-Marseille Université, Inserm, U1251-MMG, Marseille Medical Genetics, Marseille, France
  2. 2 APHM, Hôpital Timone Enfants, Département de Génétique Médicale, Marseille, France
  3. 3 APHM, Hôpital de la Conception, Laboratoire de Biochimie, Marseille, France
  4. 4 APHM, Centre de référence des maladies neuromusculaires et de la SLA, CHU La Timone, Marseille, France
  5. 5 GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science), Marseille, France
  1. Correspondence to Dr Mathieu Cerino, INSERM, Marseille Medical Genetics, U1251, Aix-Marseille Université, Marseille 13284, France; mathieu.cerino{at}

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In our original publication by Sevy et al,1 we described a cohort of patients affected with distal myopathy analysed by a large gene panel approach. Given the rapid evolution of genomic diagnostic data and interpretation standards, we now provide the re-evaluation of genetic diagnoses for this cohort. We reported in 2016 a patient (P8 in table 1) carrying a variant in KBTBD13 which led us to give a probable diagnosis implicating this gene.1 Based on the initial medical history of the patient, this case was considered as sporadic. Despite efforts to collect further family samples, only the index patient’s DNA was available for analysis at that time. Once further investigation of this family became possible, clinical examination of the patient’s mother revealed a similar phenotype as her son, suggesting an autosomal dominant inheritance. Targeted sequencing showed that she did not carry the KBTBD13 variant, arguing against the initially suggested pathogenic role of this variant. Patient P8 and the patient’s mother were then analysed by a newly designed gene panel with improved gene coverage and a larger list of genes using an actualised version of the Gene Table of Neuromuscular Disorder.2

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Table 1

Pathogenicity reassessment of each identified variant for Sevy et al publication1 patients with definite, probable and possible diagnoses

Doing so, we identified the c.1483G>A (p.(Gly495Arg)) variant in the DNM2 gene (NM_001005361.3) for both of these patients. Even though this variant is not yet described in the literature, we classified this variant …

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  • Contributors MC, MB and MK designed the gene panel and performed the molecular diagnosis by analysing the sequencing data. ES-C, AS and SA performed the clinical diagnosis of the patients. MC wrote the manuscript in consultation with MK, SG, NL, NB-P and ES-C.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.