title: 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: Inserm UMR_S 910: Génétique des maladies neuromusculaires et des laminopathies, Faculty of Medecine, Marseille, France. caroline.gaudy@ap-hm.fr
authors: Caroline
authors: C
authors: Gaudy-Marqueste
authors: Amandine
authors: A
authors: Boyer
authors: Claire
authors: C
authors: Navarro
authors: Cécile
authors: C
authors: Rouzier
authors: Jean Robert
authors: JR
authors: Harley
authors: Pierre-Jean
authors: PJ
authors: Weiller
authors: Jean-Jacques
authors: JJ
authors: Grob
authors: Nicolas
authors: N
authors: Levy
authors: Annachiara
authors: A
authors: De Sandre-Giovannoli
mesh_terms: D015331:Cohort Studies; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics*; D000097682:Lamin B Receptor
chemical_list: D034904:Lamin Type A; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor; C494847:LMNA protein, human; C120130:ZMPSTE24 protein, human