LMNA, ZMPSTE24, and LBR are not mutated in scleroderma.

Abstract

Scleroderma is a rare multisystemic disease of unknown etiology presumed to develop in genetically predisposed patients. Since patients affected with scleroderma develop clinical features similar to those observed in some laminopathies, we decided to screen at the genomic level a cohort of 27 patients affected with either localized or systemic scleroderma for mutations in three lamin-related genes: LMNA, encoding A-type lamins; ZMPSTE24, encoding a protease involved in lamin A processing; and LBR, encoding the lamin B receptor. No mutation was retrieved, whereas 25 polymorphic sequence variations were identified, 7 of which were unreported. Functional analyses performed for three of these allowed exclusion of an impact on splicing. Multiplex ligation-dependent probe amplification analysis showed no LMNA deletion or duplication. Altogether our results suggest that LMNA, ZMPSTE24, and LBR sequence variations are not major genetic determinants involved in scleroderma pathogenesis.

• Authors: Caroline Gaudy-Marqueste, Amandine Boyer, Claire Navarro, Cécile Rouzier, Jean Robert Harley, Pierre-Jean Weiller, Jean-Jacques Grob, Nicolas Levy, Annachiara De Sandre-Giovannoli
• Journal: Genetic testing and molecular biomarkers (Genet Test Mol Biomarkers) Vol. 13 Issue 5 Pg. 635-9 (Oct 2009) ISSN: 1945-0257 [Electronic] United States
• PMID: 19645629 (Publication Type: Journal Article)

Chemical References

• LMNA protein, human
• Lamin Type A
• Membrane Proteins
• Receptors, Cytoplasmic and Nuclear
• lamin B receptor
• Metalloendopeptidases
• ZMPSTE24 protein, human

Topics

• Cohort Studies
• Humans
• Lamin Type A (genetics)
• Membrane Proteins (genetics)
• Metalloendopeptidases (genetics)
• Receptors, Cytoplasmic and Nuclear (genetics)
• Scleroderma, Systemic (genetics)