SLOS carrier frequency in Poland as determined by screening for Trp151X and Val326Leu DHCR7 mutations

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations in the DHCR7 gene. Previous studies estimated the prevalence of SLOS between 1 in 10,000 to 1 in 70,358 based on case frequency surveys. Although panethnic, SLOS appears to be most frequent in Central European populations (Czech Republic 1 in 10,000, Slovakia 1 in 15,000 – 1 in 20,000). In Polish individuals with SLOS two DHCR7 mutations, c.452G > A (p.Trp151X) and c.976G > T (p.Val326Leu), account for 65.2% of all observed DHCR7 mutations. We analyzed 2169 samples for the p.Trp151X mutation and 2087 for the p.Val326Leu mutation. The combined carrier frequency of these two mutations of was 2.40 ± 0.32%, yielding a calculated incidence of SLOS in Poland of 2.5 4 × 10−4–4.3 5 × 10−4 (1 in 2,300 to 1 in 3,937) placing SLOS among the most common recessive genetic disorders in Poland.