Prevalence of Smith-Lemli-Opitz Syndrome Carriers and the Spectrum of DHCR7 Pathogenic Variants in Representative Czech and Hungarian Population Cohorts.
Level 4 - case-series / case-control
Retrospective cross-sectional genetic laboratory cohort analysis without a prospective control group
PubMed 41751549 · doi:10.3390/genes17020164
What was done
A retrospective cross-sectional analysis of next-generation sequencing data was conducted using records from 55,289 individuals tested across Czech and Hungarian genetic laboratories to determine the carrier frequency for Smith-Lemli-Opitz syndrome (SLOS) and describe the mutational spectrum of pathogenic variants in the DHCR7 gene.
What was found
Causative DHCR7 variants were identified on 1,567 alleles across the 55,289 tested individuals, resulting in an overall SLOS carrier frequency of 2.83%. A total of 31 distinct DHCR7 variants were identified, with c.452G>A being the most prevalent, representing 1.8% of all detected alleles. This mutational spectrum differed from broader non-Finnish European data in gnomAD 4.1.0, where c.964-1G>C is more frequent.
Why it matters
The findings identify a high carrier rate (~1 in 35 individuals) in Central European cohorts and demonstrate regional differences in predominant DHCR7 mutations compared to standard reference databases, informing population-specific carrier screening strategies.
Limits
The dataset relies on individuals referred to genetic testing laboratories rather than a randomly selected general-population cohort, introducing potential ascertainment bias. The abstract does not report separate carrier rates for the Czech versus Hungarian sub-cohorts or provide clinical/phenotypic follow-up data.
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