title: Spectrum of DHCR7 mutations in Slovak patients with Smith-Lemli-Opitz syndrome and detection of common mutations by PCR-based assays.
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.
authors.affiliation: Centre of Medical Genetics, University Hospital, Mickiewiczova 13, 813 69 Bratislava, Slovakia. katekole@centrum.sk
authors.forename: Katarína
authors.initials: K
authors.lastname: Kolejáková
authors.forename: Robert
authors.initials: R
authors.lastname: Petrovic
authors.forename: Ján
authors.initials: J
authors.lastname: Futas
authors.forename: Peter
authors.initials: P
authors.lastname: Turcáni
authors.forename: Darina
authors.initials: D
authors.lastname: Durovcíková
authors.forename: Ján
authors.initials: J
authors.lastname: Chandoga
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D018154:Slovakia; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase