ABSTRACT
Carrier screening involves detection of carrier status for genes associated with recessive conditions. A negative carrier screening test result bears a nonzero residual risk (RR) for the individual to have an affected child. The RR depends on the prevalence of specific conditions and the detection rate (DR) of the test itself. Herein, we provide a detailed approach for calculating DR and RR. DR was calculated on the basis of the sum of disease allele frequencies (DAFs) of pathogenic variants found in published literature. As a proof of concept, DAF data for cystic fibrosis were compared with society guidelines. The DAF data calculated by this method were consistent with the published cystic fibrosis guideline. In addition, we compared DAF for four genes (ABCC8, ASPA, GAA, and MMUT) across three laboratories, and outlined the likely reasons for discrepancies between these laboratories. The utility of carrier screening is to support couples with information while making reproductive choices. Accurate development of DR and RR is therefore critical. The method described herein provides an unbiased and transparent process to collect, calculate, and report these data.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Cystic Fibrosis/prevention & control , Gene Frequency , Genetic Carrier Screening/methods , Amidohydrolases/genetics , Consanguinity , Family , Genetic Counseling/methods , Humans , Mass Screening/methods , Sulfonylurea Receptors/genetics , alpha-Glucosidases/geneticsABSTRACT
In 2% to 3% of cases, prenatal microarray testing detects deletions and duplications in a fetus' genome that are undetected by conventional cytogenetics. Many of these changes are associated with variable or uncertain symptomatology. Little is known about how couples experience uncertain results. This study analyzed 24 interviews with members of 12 heterosexual U.S. couples who received pathogenic or uncertain microarray prenatal testing results. Researchers used narrative analysis to examine couples' understanding and incorporation of findings into decision making regarding pregnancy termination. Couples felt unprepared for these findings and frustrated because scant information was available to aid interpretation. Women sought information and made decisions, and men marginalized their distress to support their wives. A shift in voice from first to second person indicated attempts to normalize emotional responses by making the process "common" to all couples. Families pursuing highly sensitive prenatal testing may need expert guidance to support decision making.
