title: A simple PCR-based assay allows detection of a common mutation, IVS8-1G-->C, in DHCR7 in Smith-Lemli-Opitz syndrome.
abstract: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple malformation disorder. A deficiency of the enzyme 7-dehydrocholesterol delta 7-reductase (DHCR7) is the primary abnormality in SLOS. The gene encoding DHCR7 has been cloned, and we have identified a mutation affecting the splice acceptor site 5' of exon 9 that occurs frequently in affected individuals. We developed a novel PCR-based assay to detect this common mutation in DHCR7. Using this assay, heterozygosity was detected for this mutation in 18 of 26 and homozygosity in 1 of 26 unrelated affected individuals. The high frequency of this mutation is suggestive of either a founder effect in our group of patients or a mutational hotspot. The simplicity and reliability of this assay will allow it to be used as a clinical test to aid in diagnosis of atypical cases, in carrier testing, in prediction of prognosis based on genotype, and in prenatal molecular genetic diagnostic testing.
authors.affiliation: Department of Pediatrics, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Battaile
authors.forename: C L
authors.initials: CL
authors.lastname: Maslen
authors.forename: C A
authors.initials: CA
authors.lastname: Wassif
authors.forename: P
authors.initials: P
authors.lastname: Krakowiak
authors.forename: F D
authors.initials: FD
authors.lastname: Porter
authors.forename: R D
authors.initials: RD
authors.lastname: Steiner
mesh_terms: D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D012326:RNA Splicing; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*
chemical_list: D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase