RESTRICTIVE DERMOPATHY

ZMPSTE24 GENE ANALYSIS

Restrictive Dermopathy (RD) is a rare autosomal recessive disorder characterized by intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, joint contractures, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death due to pulmonary hypoplasia and respiratory insufficiency (see review by Smigiel et al. 2010 Am J Med Genet Part A 152A;447–452). The syndrome results from homozygous or compound heterozygous truncating variants in the zinc metalloproteinase (ZMPSTE24) gene, encoding an enzyme necessary for the correct processing and maturation of lamin A. Rare variants in the LMNA gene have also been reported in four patients with an RD phenotype; a patient with a heterozygous c.1824C>T (p.G608G) LMNA splicing variant in exon 11 and a patient with a heterozygous c.1968+1G>A LMNA splicing variant in intron 11 (Navarro et al. 2004 Hum Mol Genet 13:2493-2503), and two patients with a homozygous p.R435C LMNA missense variant in exon 7 (Starke et al. 2013 Aging (Albany NY) 5:445-459; Youn et al. 2010 Clin Genet 78:199-200).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.