Spectrum of DHCR7 mutations in Slovak patients with Smith-Lemli-Opitz syndrome and detection of common mutations by PCR-based assays

Gen Physiol Biophys. 2009 Mar;28(1):8-15.

Abstract

The Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disorder associated with multiple developmental malformations, is caused by a large spectrum of mutations in the DHCR7 gene. Mutations in the DHCR7 gene lead to a 7-dehydrocholesterol reductase deficiency, which is the final enzyme in the pathway of the cholesterol biosynthesis. Reduced cholesterol levels and elevated concentrations of its precursor 7-dehydrocholesterol in plasma and tissues are the major biochemical hallmarks of this disorder. In all patients a biochemical analysis of blood sterols using the gas chromatography/mass spectrometry was performed to confirm the clinical diagnosis of SLOS. We have also determined the mutational spectrum of DHCR7 gene in 17 Slovak patients. We identified six different mutations: nonsense mutation W151X and missense mutations V326L, L109P, G410S, R352Q, Y432C. Mutations W151X and V326L accounted for 76% of the SLOS alleles in Slovak population. The Slovak mutational spectrum is similar to that observed in other Central European countries. We also report simple polymerase chain reaction (PCR)-based assays that allow efficient and rapid mutation analysis.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cholesterol / blood
  • Codon, Nonsense*
  • DNA Mutational Analysis / methods
  • Female
  • Gene Frequency
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation, Missense*
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • Polymerase Chain Reaction / methods
  • Slovakia
  • Smith-Lemli-Opitz Syndrome / genetics*

Substances

  • Codon, Nonsense
  • Cholesterol
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase