title: Photosensitive Smith-Lemli-Opitz syndrome is not caused by a single gene mutation: analysis of the gene encoding 7-dehydrocholesterol reductase in five U.K. families.
abstract: BACKGROUND
  Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by a disorder in cholesterol metabolism. SLOS is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, an enzyme that catalyses the final step in cholesterol biosynthesis. We have previously established the clinical and photobiological features of the photosensitivity that is frequently a feature of SLOS.
  
  
  OBJECTIVE
  In this study, we have performed mutational analysis of the DHCR7 gene in individuals from five families with SLOS. In each family, one member was affected by severe photosensitivity as a manifestation of SLOS.
  
  
  METHODS
  Fifteen samples (including family controls) were screened using polymerase chain reaction amplification and direct automated sequencing.
  
  
  RESULTS
  Six different DHCR7 mutations were identified of which five were single point mutations that caused missense amino acid substitutions (P51H, T93M, L99P, E448K and R450L). The other was a splice site mutation (G-->C in splice acceptor site) affecting the intron 8-exon 9 splice junction (IVS8-1 G-->C). This splice site mutation and four of the five missense mutations have been previously published as causal in SLOS but the P51H is a novel mutation which has not previously been reported.
  
  
  CONCLUSIONS
  This is the first study in which DHCR7 gene mutational analysis has been performed on SLOS subjects with severe photosensitivity and indicates that no single mutation is responsible for the photosensitivity which characterizes this disorder.
authors.affiliation: Department of Dermatology, Royal Liverpool University Hospital, Liverpool L7 8XP, U.K.
authors.forename: A V
authors.initials: AV
authors.lastname: Anstey
authors.forename: R M
authors.initials: RM
authors.lastname: Azurdia
authors.forename: L E
authors.initials: LE
authors.lastname: Rhodes
authors.forename: A D
authors.initials: AD
authors.lastname: Pearse
authors.forename: P E
authors.initials: PE
authors.lastname: Bowden
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D019082:Smith-Lemli-Opitz Syndrome / Q000201:enzymology / Q000235:genetics*; D006113:United Kingdom
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase