Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F

Annalaura Torella, Marina Fanin, Margherita Mutarelli, Enrico Peterle, Francesca Del Vecchio Blanco, Rossella Rispoli, Marco Savarese, Arcomaria Garofalo, Giulio Piluso, Lucia Morandi, Giulia Ricci, Gabriele Siciliano, Corrado Angelini, Vincenzo Nigro

Research output: Contribution to journalArticle

Abstract

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-β 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.

Original languageEnglish
Article numbere63536
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - May 7 2013

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Karyopherins
Genes
muscular dystrophy
Muscle
Limb-Girdle Muscular Dystrophies
limbs (animal)
genes
Gene encoding
importins
Exome
Chromosomes
muscles
missense mutation
Cell Nucleus Active Transport
Muscular Dystrophies
Muscle Weakness
Missense Mutation
skeletal muscle
Amino Acids
Skeletal Muscle

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Torella, A., Fanin, M., Mutarelli, M., Peterle, E., Del Vecchio Blanco, F., Rispoli, R., ... Nigro, V. (2013). Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. PLoS One, 8(5), [e63536]. https://doi.org/10.1371/journal.pone.0063536

Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. / Torella, Annalaura; Fanin, Marina; Mutarelli, Margherita; Peterle, Enrico; Del Vecchio Blanco, Francesca; Rispoli, Rossella; Savarese, Marco; Garofalo, Arcomaria; Piluso, Giulio; Morandi, Lucia; Ricci, Giulia; Siciliano, Gabriele; Angelini, Corrado; Nigro, Vincenzo.

In: PLoS One, Vol. 8, No. 5, e63536, 07.05.2013.

Research output: Contribution to journalArticle

Torella, A, Fanin, M, Mutarelli, M, Peterle, E, Del Vecchio Blanco, F, Rispoli, R, Savarese, M, Garofalo, A, Piluso, G, Morandi, L, Ricci, G, Siciliano, G, Angelini, C & Nigro, V 2013, 'Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F', PLoS One, vol. 8, no. 5, e63536. https://doi.org/10.1371/journal.pone.0063536
Torella A, Fanin M, Mutarelli M, Peterle E, Del Vecchio Blanco F, Rispoli R et al. Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. PLoS One. 2013 May 7;8(5). e63536. https://doi.org/10.1371/journal.pone.0063536
Torella, Annalaura ; Fanin, Marina ; Mutarelli, Margherita ; Peterle, Enrico ; Del Vecchio Blanco, Francesca ; Rispoli, Rossella ; Savarese, Marco ; Garofalo, Arcomaria ; Piluso, Giulio ; Morandi, Lucia ; Ricci, Giulia ; Siciliano, Gabriele ; Angelini, Corrado ; Nigro, Vincenzo. / Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F. In: PLoS One. 2013 ; Vol. 8, No. 5.
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