Refining NGS diagnosis of muscular disorders

Mathieu Cerino (1, 2) , Emmanuelle Salort-Campana (1, 2) , Svetlana Gorokhova (1, 2) , Amandine Sevy (2) , Nathalie Bonello-Palot (1, 2) , Nicolas Levy (1, 2) , Shahram Attarian (1, 2) , Marc Bartoli (1) , Martin Krahn (1, 2)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
2 TIMONE - Hôpital de la Timone [CHU - APHM]

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

Domaines: Génétique

Mathieu Cerino, Emmanuelle Salort-Campana, Svetlana Gorokhova, Amandine Sevy, Nathalie Bonello-Palot, et al.. Refining NGS diagnosis of muscular disorders. Journal of Neurology, Neurosurgery and Psychiatry, 2020, jnnp-2018-319254. ⟨10.1136/jnnp-2018-319254⟩. ⟨hal-02959292⟩