How Often Does Prenatal Carrier Screening Detect Pathogenic Risk Alleles in a Parent?
BACKGROUND AND PURPOSE:
Carrier screening can successfully identify couples at reproductive risk
Newer screening tests may detect genetic findings that are relevant to health of the screened individual, not just future children
Reiner et al. (Genetics in Medicine, 2022) assessed the frequency of pathogenic genotypes in presumed healthy individuals undergoing carrier screening
Retrospective cohort analysis
Samples submitted for testing via sequencing carrier screening panels
Pathogenic genotype category: At least 2 pathogenic or likely pathogenic variants reported in a single gene associated with an autosomal recessive condition | Single clinically significant variant in an X-linked gene in males | 0 copies of the SMN1 gene
At risk category: Heterozygous variants in genes that conferred increased risk for adult-onset disease (e.g., FMR1 premutation alleles) | Pathogenic variants in genes associated with cancer risk
Prevalence of pathogenic genotypes associated with moderate to profound autosomal recessive or X-linked conditions in screened individuals
Prevalence of heterozygote risk alleles
73,755 targeted carrier screens
Identified individuals with pathogenic genotypes: 79 (0.11%)
There were also 10 cases of chromosome X dosage abnormalities suggestive of a sex chromosome abnormality
Heterozygote risk alleles represented most ancillary findings in this cohort
Female carriers of FMR1 premutation alleles: 280
Heterozygous females with pathogenic DMD variants: 15
Heterozygotes with pathogenic variants in genes that may confer increased risk for somatic malignancies in the heterozygous state: 174
Approximately 0.1% of individuals screened had suggested pathogenic genotypes
Additionally, nearly 1% of screened individuals were carriers of risk alleles
The authors state
Even currently actionable diseases or variants with strong evidence of risk, such as breast cancer risk in heterozygotes with pathogenic ATM variants and cardiomyopathy risk in heterozygous females with pathogenic DMD variants, merit consideration because the subject of disclosure should not be separated from discussions on patient consent and privacy
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