Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features – a case report

BMC Medical Genetics

Case Report

Manlio Giacanelli¹  Ludovico Lispi¹  Antonio Petrucci¹  Marco Savarese²  Vincenzo Nigro³  Roberto Massa⁴  Guja Astrea⁵  Filippo M. Santorelli⁵  Anna Rubegni⁵  Denise Cassandrini⁵  Rosanna Trovato⁵ 

[1] Center for Neuromuscular and Neurological Rare Diseases, S. Camillo-Forlanini Hospital, Rome, Italy;Department of Biochemistry, Biophysics and General Pathology (Medical Genetics), Second University of Naples, Naples, Italy;Department of Biochemistry, Biophysics and General Pathology (Medical Genetics), Second University of Naples, Naples, Italy;Telethon Institute of Genetics and Medicine, Naples, Italy;Department of Systems Medicine (Neurology), University of Tor Vergata, Rome, Italy;Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy;

关键词: Core myopathies;    MYH7;    RYR1;    Muscle MRI;    Next-generation sequencing;   

DOI  :  10.1186/s12881-016-0288-0

 received in 2015-11-17, accepted in 2016-03-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMyosin 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 presentationThe 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© Astrea et al. 2016