A Simple PCR-Based Assay Allows Detection of a Common Mutation,IVS8-1G→C,in DHCR7 in Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple malformation disorder. A deficiency of the enzyme 7-dehydrocholesterol Δ⁷-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.