Aiutaci a camminare, aiutaci a vivere

Limb-girdle muscular dystrophies (LGMD) are genetically and clinically heterogeneous conditions. We investigated a large family with autosomal dominant transmission pattern, previously classified as LGMD1F and mapped to chromosome 7q32. Affected members are characterized by muscle weakness affecting earlier the pelvic girdle and the ileopsoas muscles. We sequenced the whole exome of four family members and identified a shared heterozygous frame-shift variant in the Transportin 3 (TNPO3) gene, encoding a member of the importin-b super-family. The TNPO3 gene is mapped within the LGMD1F critical interval and its 923-amino acid human gene product is also expressed in skeletal muscle. In addition, we identified an isolated case of LGMD with a new missense mutation in the same gene. We localized the mutant TNPO3 around the nucleus, but not inside. The involvement of gene related to the nuclear transport suggests a novel disease mechanism leading to muscular dystrophy. Citation: Torella A, Fanin M, Mutarelli M, Peterle E, Del Vecchio Blanco F, et al. (2013) Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. PLoS ONE 8(5): e63536. doi:10.1371/journal.pone.0063536 Editor: Paul McNeil, Medical College of Georgia, United States of America Received February 15, 2013; Accepted March 25, 2013; Published May 7, 2013 Copyright: 2013 Torella et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was mainly supported by grants from Telethon, Italy (TGM11Z06 to V.N. and GTB12001 to C.A.) and Telethon-UILDM (Unione Italiana Lotta alla Distrofia Muscolare) (GUP 10006 and GUP11006 to V.N.). This work was also supported by grants from the Association Française contre les Myopathies (13859 to M.F. and 14999/16216 to C.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: vincenzo.nigro@unina2.it . These authors contributed equally to this work.