Molecular prenatal diagnosis of Smith–Lemli–Opitz syndrome is reliable and efficient

Abstract

Smith-Lemli-Opitz (RSH) syndrome (SLOS, OMIM 270400) is a relatively common, autosomal recessive disorder of cholesterol biosynthesis with a broad spectrum of phenotypic abnormalities caused by mutations of the 7-dehydrocholesterol reductase gene (DHCR7) on chromosome 11. Prenatal diagnosis can be established by detection of elevated 7-dehydrocholesterol or of SLOS-causing mutations in the DHCR7 gene. We report here our experience with molecular prenatal diagnosis of SLOS. Mutation analysis of the DHCR7 gene was performed in chorionic villus samples of 13 pregnancies of couples with a family history of SLOS and known SLOS genotypes. This approach is accurate and reliable. If facilities for biochemical analysis are not available, or in cases with ambiguous biochemical patterns, molecular prenatal diagnosis is an attractive, alternative option.

DHCR7 nonsense mutations and characterisation of mRNA nonsense mediated decay in Smith-Lemli-Opitz syndrome

“…This figure is a compilation of data of the W151X patients presented above, unpublished data, and previously reported cases. [23][24][25][26][27][28][29][30][31][32] As expected, IVS8-1GRC and W151X homozygous as well as W151X/IVS8-1GRC patients are severely affected. There were only two patients with this genotype who had severity scores less than 50.…”

Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy

“…It results from deficiency of 7-dehydrocholesterol reductase, due to mutation of the gene on chromosome 11 [47]. This leads to defective cholesterol synthesis and elevation of 7-dehydrocholesterol in plasma and tissues [48].…”

Fetal cardiac abnormalities: Genetic etiologies to be considered

“…DHCR7 is the only gene in which pathogenic variants are known to cause SLOS (Table ) . Molecular prenatal diagnosis is suggested when there are family mutations or in the context of ambiguous biochemical patterns . Prenatal testing for SLOS is warranted in the presence of family history or multiple malformations typical for SLOS, especially if there is additional IUGR or low MSuE3 …”