A c.89G>C p.(Gly30Ala) Variant in the DHCR7 Gene as a Cause of a Mild Phenotype in the Smith-Lemli-Opitz Syndrome.

backgroundSmith-Lemli-Opitz syndrome (SLOS) is a common autosomal recessive disorder caused by pathogenic variants in the DHCR7 gene, resulting in a deficiency of the enzyme 7-dehydrocholesterol reductase. Two forms of SLOS are recognized based on the severity of associated symptoms. Type I is characterized by a milder phenotype, whereas type II is more severe and frequently results in fetal loss or early neonatal death. We observed two unrelated patients: a 5-year-old boy and a 3.5-year-old girl, with elevated 7-DHC levels, a milder phenotype, and an identical genotype.

methodsVariants were confirmed by Sanger sequencing.

resultsA rare heterozygous likely pathogenic variant, c.89G>C p.(Gly30Ala), and a pathogenic variant, c.964-1G>C, in the trans position in the DHCR7 gene were identified in both patients.

conclusionThe two unique patients presented here suggest that the c.89G>C p.(Gly30Ala) variant is associated with a mild SLOS phenotype, which may be overlooked and unrecognized in clinical practice. Information about this rare DHCR7 variant is important for diagnostic awareness of SLOS, especially within the Central European population. We present clinical data and a literature review of the DHCR7 variants associated with the mild SLOS phenotype.