Available online at www.sciencedirect.com Neuromuscular Disorders 28 (2018) 633–638 www.elsevier.com/locate/nmd Case report A new mutation of the SCGA gene is the cause of a late onset mild phenotype limb girdle muscular dystrophy type 2D with axial involvement Lidia Gonzalez-Quereda a,1 , Eduard Gallardo b,1 , Ana Töpf c , Alicia Alonso-Jimenez d , Volker Straub c , Maria Jose Rodriguez e , Cinta Lleixa d , Isabel Illa b , Pia Gallano a,* , Jordi Diaz-Manera b,* a Genetics Department, Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER CB06/07/0011), Hospital de la Santa Creu I Sant Pau, IIB Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona, Spain b Neuromuscular disorders Unit, Neurology Department, Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER CB06/05/0030), Universitat Autònoma de Barcelona, Hospital de la Santa Creu I Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona, Spain c The John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular disorders, Institute of Genetic Medicine, Central Parkway, Newcastle Upon Tyne, UK d Neuromuscular disorders Unit, Neurology department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain e Genetics Department, Hospital de la Santa Creu I Sant Pau, IIB Sant Pau, Barcelona, Spain Received 25 March 2018; received in revised form 21 May 2018; accepted 7 June 2018 Abstract Mutations in the SGCA gene cause limb girdle muscular dystrophy type 2D (LGMD2D). We report a family with three affected siblings with a mild phenotype consisting of late onset glutei and axial muscle weakness produced by a new mutation in the SGCA gene leading to a partial expression of the alpha-sarcoglycan protein. The MRI showed muscle atrophy involving paraspinal, pelvic and thigh muscles and a dystrophic pattern was observed in the muscle biopsy. Exome sequencing revealed a homozygous intronic deletion of SGCA and mRNA analysis showed the presence of three different transcripts. The presence, though in a lower proportion, of wild type transcript leads to a milder presentation of the disease. Although clinical symptoms did not entirely correspond with a sarcoglycanopathy, a compatible muscle MRI drove us to look for changes in the sarcoglycan genes. These cases are an example of how clinical, radiological and pathological data enriches the interpretation of exome analysis. © 2018 Elsevier B.V. All rights reserved. Keywords: Axial myopathy; SGCA; Sarcoglycans; NGS. 1. Introduction Mutations in the SGCA gene lead to a deficit or absence of the alpha-sarcoglycan protein which is one of the members of the dystrophin-glycoprotein complex (DGC) [1]. DGC complex is involved in the stability of muscle fiber membrane by linking the cytoskeleton to the extracellular matrix [2]. * Corresponding authors. E-mail addresses: pgallano@santpau.cat (P. Gallano), jdiazm@santpau.cat (J. Diaz-Manera). 1 These authors have equally contributed to the work. Mutations in DGC genes induce instability of the sarcolemma during muscle contraction that leads to muscle injury [3]. Patients with mutations in SCGA gene develop an auto- somal recessive muscle dystrophy known as LGMD2D [4]. Series reported show a homogeneous clinical picture charac- terized by childhood onset, quick progression of muscle weak- ness and loss of ambulation before the adulthood in most of the cases [5]. However, some milder adult onset cases have been reported. This clinical variability could be related with the type of mutation [6]. Truncating mutations are commonly associated with severe progression while missense mutations are associated with milder clinical presentations. https://doi.org/10.1016/j.nmd.2018.06.002 0960-8966/© 2018 Elsevier B.V. All rights reserved. þÿDescargado para Anonymous User (n/a) en Fundació de Gestió Sanitària de l Hospital de Santa Creu i Sant Pau de C Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.