title: Novel frameshifting mutations of the ZMPSTE24 gene in two siblings affected with restrictive dermopathy and review of the mutations described in the literature.
abstract: Restrictive dermopathy (RD) is a rare, severe, lethal genodermatosis in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence. To date, about 60 cases of RD were described. The signs of the disease are very characteristic and include intrauterine growth retardation, thin, tightly adherent translucent skin, superficial vessels, typical facial dysmorphism as well as generalized joint contractures. The syndrome is caused in most cases by ZMPSTE24 autosomal recessive mutations, or, less frequently, by LMNA autosomal dominant mutations. We report on two brothers affected with RD, who died in the neonatal period. Molecular analyses were performed in the second child, for whom biological material was available, and both parents. Compound heterozygous frameshifting mutations were identified in exon 1 (c.50delA) and exon 5 (c.584_585delAT) of the ZMPSTE24 gene. The autosomal recessive inheritance was confirmed by the parents' genomic analysis. Besides, a review of the mutations causing RD is made.
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland. smigiel@gen.am.wroc.pl
authors.forename: Robert
authors.initials: R
authors.lastname: Smigiel
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jakubiak
authors.forename: Vera
authors.initials: V
authors.lastname: Esteves-Vieira
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szela
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jurek
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Annachiara
authors.initials: A
authors.lastname: De Sandre-Giovannoli
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D005091:Exons; D005192:Family Health; D017809:Fatal Outcome; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D035781:Siblings; D012868:Skin Abnormalities / Q000235:genetics*
chemical_list: D034882:Lamins; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human