Carrier frequency of the common mutation IVS8-IG > C in DHCR7 and estimateof the expected incidence of Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental r etardation syndrome of variable severity with an incidence previously estim ated at 1 in 20,000-60,000 based on case frequency surveys, Identification of the gene defect in SLOS has made it possible to calculate the carrier fr equency and estimate disease incidence using molecular methods to identify carriers. Using a previously described PCR-RFLP assay we screened 1503 anon ymous blood samples from random newborn screening blood spot cards for the presence of the common SLOS mutation IVS8-1G>C in order to determine the ca rrier frequency. Sixteen carriers were identified in the 1503 samples. Sinc e the frequency of the IVS8-1G>C mutation among all SLOS gene mutations is known, the overall carrier frequency for all mutations can be calculated, T he calculated carrier frequency for all mutations based on this result is 1 in 30, predicting an SLOS incidence of 1 in 1590 to 1 in 13,500. The curre nt incidence estimate may, therefore, significantly underestimate the true incidence of SLOS. This discrepancy between calculated and observed inciden ce could be due to undiagnosed mild cases, misdiagnosed severe cases, death prior to diagnosis, or fetal loss, More comprehensive incidence studies ar e needed to determine if SLOS is as common as predicted by the very high (1 in 30) carrier frequency determined in this study. (C) 2001 Academic Press .