Detection of a common mutation in the RSH or Smith-Lemli-Opitz syndrome bya PCR-RFLP assay: IVS8-1G -> C is found in over sixty percent of US propositi

The RSH or Smith-Lemli-Opitz syndrome (SLOS) is a relatively common autosom al recessive disorder of cholesterol biosynthesis resulting from a deficien cy of the enzyme 7-dehydrocholesterol Delta 7-reductase (7-DHCR), Mutations in 7-DHCR gene cause SLOS. among these, a G -> C transversion in the splic e acceptor site of exon 9 (IVS8-1G -> C) was suspected to be a frequent mut ation, having been detected in about 18% of SLOS patients so far. This muta tion results in the elimination of a AIwN1 restriction endonuclease site. W e report a simple PCR-RFLP assay to detect the IVS8-1 G -> C mutation. Usin g this method, we identified the IVS8-1G -> C mutation in 21 of 33 SLOS pro positi. This mutation was detected in one of 90 normal adult Caucasian Amer icans; but not among 121 Africans from Sierra Leone, 120 Caucasians from Fi nland, 95 Chinese or 103 Japanese adults. The results of this study provide further evidence that IVS8-1G -> C transversion is a very common mutation in SLOS patients from the US and that the carrier rate in US caucasians may be high. The simple PCR-RFLP assay developed makes identification of this mutation convenient for diagnosis and for carrier detection, (C) 2000 Wiley -Liss, Inc.