Farzad Fatehi1, Shahriar Nafissi2, J Andoni Urtizberea3, Véronique Blanck-Labelle4, Nicolas Lévy5, Martin Krahn5, Mohamad Baker Dbouk1, Shahram Attarian6. 1. Iranian Center of Neurological Research, Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2. Iranian Center of Neurological Research, Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nafisi@sina.tums.ac.ir. 3. Centre GNMH, Hôpital Marin de Hendaye, APHP, 64700 Hendaye, France. 4. APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France. 5. APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France; Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385 Marseille, France. 6. Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385 Marseille, France; Reference Center for Neuromuscular Disorders and ALS CHU La Timone Marseille, France.
Abstract
BACKGROUND: Dysferlinopathy is caused by a very wide range of autosomal recessively inherited mutations of the Dysferlin gene. It causes a spectrum of muscle diseases including limb-girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy (MM). We describe the clinical course and mutational analyses of 15 Iranian patients with dysferlinopathy from 9 different families. METHODS: Genomic DNA was extracted from peripheral blood and 55 exons and flanking intronic boundaries of the dysferlin gene (DYSF; NM_003494.2) were screened for mutations and analyzed. RESULTS: From 15 studied patients in 9 families, 5 patients were male. Seven families had consanguineous marriage. Median age of onset was 16.8; and the median age of diagnosis was 26.6. The onset was clearly distal in 7 patients, and proximal in 6 patients. Three patients had partial biceps atrophy and 13 showed prominent calf muscle wasting. Foot plantar flexors, deep finger flexors and hip adductors were predominantly involved. Genetic testing showed homozygous mutation of dysferlin gene in 9 probands, 5 of which were not previously reported. CONCLUSION: This work, in fact, may help shed some light on the pattern of this morbidity in Iran, an effort that may have not been attempted so far.
BACKGROUND:Dysferlinopathy is caused by a very wide range of autosomal recessively inherited mutations of the Dysferlin gene. It causes a spectrum of muscle diseases including limb-girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy (MM). We describe the clinical course and mutational analyses of 15 Iranian patients with dysferlinopathy from 9 different families. METHODS: Genomic DNA was extracted from peripheral blood and 55 exons and flanking intronic boundaries of the dysferlin gene (DYSF; NM_003494.2) were screened for mutations and analyzed. RESULTS: From 15 studied patients in 9 families, 5 patients were male. Seven families had consanguineous marriage. Median age of onset was 16.8; and the median age of diagnosis was 26.6. The onset was clearly distal in 7 patients, and proximal in 6 patients. Three patients had partial biceps atrophy and 13 showed prominent calf muscle wasting. Foot plantar flexors, deep finger flexors and hip adductors were predominantly involved. Genetic testing showed homozygous mutation of dysferlin gene in 9 probands, 5 of which were not previously reported. CONCLUSION: This work, in fact, may help shed some light on the pattern of this morbidity in Iran, an effort that may have not been attempted so far.
Authors: Marco Savarese; Jaakko Sarparanta; Anna Vihola; Per Harald Jonson; Mridul Johari; Salla Rusanen; Peter Hackman; Bjarne Udd Journal: Acta Myol Date: 2020-12-01