Spectrum of DHCR7 mutations in Slovak patients with Smith-Lemli-Opitz syndrome and detection of common mutations by PCR-based assays

Abstract

Abstract. The Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disorder associated with multiple developmental malformations, is caused by a large spectrum of mutations in the DHCR7 gene. Mutations in the DHCR7 gene lead to a 7-dehydrocholesterol reductase deficiency, which is the final enzyme in the pathway of the cholesterol biosynthesis. Reduced cholesterol levels and elevated concentrations of its precursor 7-dehydrocholesterol in plasma and tissues are the major biochemical hallmarks of this disorder. In all patients a biochemical analysis of blood sterols using the gas chromatography/mass spectrometry was performed to confirm the clinical diagnosis of SLOS. We have also determined the mutational spectrum of DHCR7 gene in 17 Slovak patients. We identified six different mutations: nonsense mutation W151X and missense mutations V326L, L109P, G410S, R352Q, Y432C. Mutations W151X and V326L accounted for 76% of the SLOS alleles in Slovak population. The Slovak mutational spectrum is similar to that observed in other Central European countries. We also report simple polymerase chain reaction (PCR)-based assays that allow efficient and rapid mutation analysis.

Smith-Lemli-Opitz Syndrome with Biallelic c.1295A&gt;G (p.Tyr432Cys) Variant in the <i>DHCR7</i> Gene in a 73-Year-Old Woman: Report of the Oldest Patient

“…Nevertheless, the aforementioned study did not include detailed data on the clinical status of the patient with compound heterozygosity for this variation. In addition to our patient and the cases reported in the aforementioned studies, a literature review revealed 2 patients from Germany and 1 patient from Slovakia with the p.Tyr432Cys variant [17,18]. A total of 9 patients with this variant (p.Tyr432Cys) were reported in the literature so far [11,[15][16][17][18].…”

“…In addition to our patient and the cases reported in the aforementioned studies, a literature review revealed 2 patients from Germany and 1 patient from Slovakia with the p.Tyr432Cys variant [17,18]. A total of 9 patients with this variant (p.Tyr432Cys) were reported in the literature so far [11,[15][16][17][18]. The clinical and genotypic findings for all cases with this variation are summarized in Table 1.…”

Smith–Lemli–Opitz syndrome among Arabs

“…Thus, it appears that the R352Q mutation in homozygosity state as well as in combination with null alleles (IVS8-1G>C and W151X) causes a severe phenotype. The R352Q mutation is also the most common mutation among SLOS patients from Japan (13) and was also reported in Slovak patients with SLOS (14). Patient 5 was found to be homozygous for the R352L.…”