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 language | English |
|---|---|
| Article number | e63536 |
| Journal | PLoS One |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 7 2013 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for LGMD1F
AU - Torella, Annalaura
AU - Fanin, Marina
AU - Mutarelli, Margherita
AU - Peterle, Enrico
AU - Del Vecchio Blanco, Francesca
AU - Rispoli, Rossella
AU - Savarese, Marco
AU - Garofalo, Arcomaria
AU - Piluso, Giulio
AU - Morandi, Lucia
AU - Ricci, Giulia
AU - Siciliano, Gabriele
AU - Angelini, Corrado
AU - Nigro, Vincenzo
PY - 2013/5/7
Y1 - 2013/5/7
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0063536
DO - 10.1371/journal.pone.0063536
M3 - Article
C2 - 23667635
AN - SCOPUS:84877119095
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e63536
ER -