A novel de nova missense LMNA mutation in a Turkish patient with laminopathies

Abstract

The laminopathies associated to the lamin A/C (LMNA) gene mutations at chromosome 1q22 region; comprise different well-characterized phenotypes. Some of the multi-systemic laminopathies are lipodystrophy, Charcot-Marie Tooth disease (CMT), Emery-Dreifuss muscular dystrophy (EDMD) and Limb Girdle muscular dystrophy 1B (LGMD1B). The LGMD1B is characterized by a symmetric proximal weakness starting from the legs, atrioventricular conduction disturbances and dysrhythmias. 17-year-old female patient had suffered from progressive muscle weakness. Patient's testing of deep-tendon reflexes were negative in neurological examination. She had positive Gower's sign and proximal muscle strength was reduced with score of 4/5. She had foot-drop gait and atrophy of lower extremities. Her feet showed a mild pescavus deformity and could not lift up by herself. Serum creatine kinase level was normal. Followed by pediatric cardiology due to first degree A–V block. Cardiac echocardiogram demonstration was normal. Nerve conduction velocity was within normal limits and electromyogram was indicative of myopathy. Muscular histology was compatible with muscular dystrophy and showed a nonspecific excess of lipid droplets. With the diagnosis of Limb Girdle muscular dystrophy 1B; LMNA gene sequence analysis including all coding exons and exon-intron boundaries was done and LMNA NM_170707.3:c.734T>C; (p.Leu245Pro) heterozygous missense mutation was detected. This mutation was first reported by from Turkish population. In silico analysis with Mutation Taster, Polyphen2, SIFT was predict this variant as a disease causing mutation. In order to show familial segregation, mother and father also were included in the study. Her parents were no carriers of the mutation. This case illustrate the necessity of correct diagnosis, evaluation, and follow up of cardiac problems due to the wide clinical spectrum and high prevalence of cardiac conduction block in patients with LGMD1B.