New mutations found by Next-Generation Sequencing screening of Spanish patients with Nemaline Myopathy

• DOI: 10.1371/journal.pone.0207296
• Publication Date: 2018-12-05T18:31:45Z
• Authors: Sarah Moreau-Le Lan; Elena Aller; Ines Calabria; Lola Gonzalez-Tar...; Cristina Cardona-Gay; Marina Martinez-M...; Maria J. Aparisi; Jorge Selles; Lydia Sagath; Inmaculada Pitarch; Nuria Muelas; Jose V. Cervera; Jose M. Millan; Laia Pedrola
• Keywords: Adult; Male; 0301 basic medicine; Science; RNA Splicing; Muscle Proteins; VARIANTS; Myopathies, Nemaline; 03 medical and health sciences; Gene Frequency; Humans; Child; Muscle, Skeletal; Alleles; Muscle Weakness; Q; R; High-Throughput Nucleotide Sequencing; General medicine, internal medicine and other clinical medicine; Actins; Pedigree; 3. Good health; Spain; Mutation; Medicine; Muscle Hypotonia; Female; NEBULIN; Research Article

Nemaline Myopathy (NM) is a rare genetic disorder that encompasses a large spectrum of myopathies characterized by hypotonia and generalized muscle weakness. To date, mutations in thirteen different genes have been associated with NM. The most frequently responsible genes are NEB (50% of cases) and ACTA1 (15-25% of cases). In this report all known NM related genes were screened by Next Generation Sequencing in five Spanish patients in order to genetically confirm the clinical and histological diagnosis of NM. Four mutations in NEB (c.17779_17780delTA, c.11086A>C, c.21076C>T and c.2310+5G>A) and one mutation in ACTA1 (c.871A>T) were found in four patients. Three of the four mutations in NEB were novel. A cDNA sequencing assay of the novel variants c.17779_17780delTA, c.11086A>C and c.2310+5G>A revealed that the intronic variant c.2310+5G>A affected the splicing process. Mutations reported here could help clinicians and geneticists in NM diagnosis.