Homozygous null mutations in ZMPSTE24 in restrictive dermopathy: Evidence of genetic heterogeneity

Z. Ahmad, S. R. Phadke, E. Arch, J. Glass, A. K. Agarwal, A. Garg

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Restrictive dermopathy (RD) results in stillbirth or early neonatal death. RD is characterized by prematurity, intrauterine growth retardation, fixed facial expression, micrognathia, mouth in the 'o' position, rigid and tense skin with erosions and denudations and multiple joint contractures. Nearly all 25 previously reported neonates with RD had homozygous or compound heterozygous null mutations in the ZMPSTE24 gene. Here, we report three new cases of RD; all died within 3 weeks of birth. One of them had a previously reported homozygous c.1085dupT (p.Leu362PhefsX19) mutation, the second case had a novel homozygous c.1020G>A (p.Trp340X) null mutation in ZMPSTE24, but the third case, a stillborn with features of RD except for the presence of tapering rather than rounded, bulbous digits, harbored no disease-causing mutations in LMNA or ZMPSTE24. In the newborn with a novel ZMPSTE24 mutation, unique features included butterfly-shaped thoracic 5 vertebra and the bulbous appearance of the distal clavicles. Skin biopsies from both the stillborn fetus and the newborn with c.1020G>A ZMPSTE24 mutation showed absence of elastic fibers throughout the dermis. This report provides evidence of genetic heterogeneity among RD and concludes that there may be an additional locus for RD which remains to be identified.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalClinical Genetics
Issue number2
StatePublished - Feb 2012


  • Lamin A/C
  • Mandibuloacral dysplasia
  • Restrictive dermopathy
  • ZMPSTE24

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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