title: Report of limb girdle muscular dystrophy type 2a in 6 Iranian patients, one with a novel deletion in CAPN3 gene.
abstract: Calpain3 is a calcium-dependent intracellular protease involved in an autosomal recessive form of muscular dystrophy known as limb-girdle muscular dystrophy type 2A. Many pathogenic mutations have been identified in calpain3, encoded by the CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles. In the present study, whole exome sequencing was performed on six unrelated Iranian families who presented with progressive muscle weakness, with a strong suspicion of Calpainopathies. Genetic analysis of CAPN3 gene revealed five causative variants which had not been reported in the Iranian population before including a novel 6 bp deletion (c.795_800delCATTGA) and four previously reported mutations (c.1939G > T, c.2243G > A, c.2257delGinsAA, and c.2380 + 2T > G). Our findings indicate that exome sequencing can be a very effective and affordable method to diagnose heterogeneous muscular dystrophies, especially in consanguineous populations such as Iran.
authors.affiliation: Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Fadaee
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Fattahi
authors.affiliation: Department of Neurology, Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Nafissi
authors.affiliation: Shiraz University of Medical Science, Shiraz, Iran; Dr. Goodarzi Medical Genetics Center, Shiraz, Iran.
authors.forename: Hamed Reza
authors.initials: HR
authors.lastname: Godarzi
authors.affiliation: Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Beheshtian
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Vazehan
authors.affiliation: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Akbari
authors.affiliation: Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.affiliation: Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran. Electronic address: hnajm12@yahoo.com.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002154:Calpain / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005190:Family; D005260:Female; D006801:Humans; D007492:Iran; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain
keywords: CAPN3; Calpain3; Iran; Limb-girdle; Muscular dystrophy; Whole exome sequencing