Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice

• DOI: 10.1038/s41436-021-01116-x
• Publication Date: 2021-03-19T10:14:54Z
• Authors: Suzanne C.E.H. Sa...; Alexander P.A. St...; Bart de Koning; Crool Velter; Anja Steyls; Melanie van Esch; Phillis Lakeman; Helger Yntema; Masoud Zamani Esteki; Christine E.M. de...; Christian Gilissen; Arthur van den Wi...; Han G. Brunner; Aimée D.C. Paulussen
• Keywords: Medical genetics; Carrier testing; Exome; Consanguineous Marriage

Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% affected offspring as consequence. Until recently, comprehensive preconception carrier testing (PCT) AR disorders was unavailable in routine diagnostics. Here we developed and implemented such test clinical care.We performed exome sequencing (ES) 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic were selected. These subsequently filtered against gene panel consisting ~2,000 genes associated known (OMIM-based). Remaining classified according American College Medical Genetics Genomics/Association Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic (class IV/V) variants, present both partners, reported.In 28 tested (28%), not previously couple or their family reported conferring offspring.ES-based PCT provides powerful diagnostic tool identify disease status Outcomes provided significant reproductive choices higher proportion these than previous tests.