Limb-girdle muscular dystrophies (LGMD) are genetically and clinically heterogeneous conditions. In this study, the authors have investigated a large family with autosomal dominant transmission pattern, previously classified as LGMD1F and mapped to chromosome 7q32. Affected members are characterised by muscle weakness affecting earlier the pelvic girdle and the ileopsoas muscles. The whole exome of four family members was sequenced and a shared heterozygous frame-shift variant in the Transportin 3 (TNPO3) gene, encoding a member of the importin-β super-family, was identified. 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, the authors identified an isolated case of LGMD with a new missense mutation in the same gene. The mutant TNPO3 was localised around the nucleus, but not inside. The involvement of a gene related to nuclear transport suggests a novel disease mechanism leading to muscular dystrophy.
