Expanded genetic carrier screening decreases the risk of conceiving an affected child in both selected and unselected populations

Does expanded carrier screening (ECS) reduce the risk of conceiving an affected child through assisted reproduction with either own or donated gametes?

Retrospective consecutive cohort study including 2380 women and 986 men tested with CarrierMap, a panel covering 2647 mutations in 311 genes. Candidates with family history of FXS, mental retardation, chromosomal abnormalities, genetic or neurological conditions are excluded from the donor program. In addition 894 matches to identify the reproductive risk were performed.

A total of 3366 expanded carrier screening test were performed. Of the 3366 individuals tested, 1458 (43.3%) were positive for at least one mutation; of them, 1091 (32.4%) carried one mutation, 306 (9.1%) two and 54 (1.6%) three; 7 individuals carried four or more mutations. The most frequent mutations found were for Nonsyndromic Hearing Loss and Deafness (GJB2 Related): 152 (10.4%); carrier frequency 1:22. Pseudocholinesterase Deficiency: 98 (6.7%); 1:34. Fragile X syndrome: 97 (6.6%); 1:34. Cystic Fibrosis: 89 (6.1%), 1:38. Familial Mediterranean fever (FMF): 82 (5.6%), 1:41. Out of the total of 894 matches 26 (2.9%) showed a high reproductive risk, since both members were carrier for mutations leading to the same disease, thus having a 1 in 4 probability to generate an effected child.

ECS effectively detects couples at a higher risk of conceiving an affected child with a positive match rate of 2.9%. This value should be higher in unselected patients, as most attempted matchings were made with donors preselected for lower carrier status by extensive family history review and initial specific genetic testing.