Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene

• DOI: 10.1093/brain/awt074
• Publication Date: 2013-03-29T23:11:27Z
• Authors: Maria J. Melià; Akatsuki Kubota; Saida Ortolano; Juan J. Vílchez; Josep Gámez; Kurenai Tanji; Eduardo Bonilla; Lluís Palenzuela; Israel Fernández-...; Anna Přistoupilová; Elena García-Arumí; Antoni L. Andreu; Carmen Navarro; Michio Hirano; Ramon Martí
• Keywords: Limb-girdle muscular dystrophy

In 2001, we reported linkage of an autosomal dominant form limb-girdle muscular dystrophy, dystrophy 1F, to chromosome 7q32.1-32.2, but the identity mutant gene was elusive. Here, using a whole genome sequencing strategy, identified causative mutation heterozygous single nucleotide deletion (c.2771del) in termination codon transportin 3 (TNPO3). This is situated within chromosomal region linked disease and encodes nuclear membrane protein belonging importin beta family. TNPO3 transports serine/arginine-rich proteins into nucleus, has been as key factor HIV-import process nucleus. The predicted generate 15-amino acid extension C-terminus protein, segregates with clinical phenotype, absent genomic sequence databases set >200 control alleles. skeletal muscle affected individuals, expression messenger RNA histological abnormalities nuclei indicate altered function. Our results demonstrate that cause expand our knowledge molecular basis dystrophies bolster importance defects envelope causes inherited myopathies.