PGT-M TO PREVENT 2 OR 3 GENETIC DISORDERS, MOSTLY DOMINANT

Abstract

To investigate the prevalence of PGT-M for 2 or 3 disorders (mg-PGT-M), increasingly requested as expanded carrier screening gains momentum. Between 2018-2021, there were 96 cases of mg-PGT-M cases from CooperGenomics (NJ). The most common genes are presented in the table below. The mode of inheritance (autosomal dominant (AR), autosomal recessive (AR) or X-Linked (XL)) as well as whether both partners carried common genes was recorded. Over the study period, of the 96 families identified, 86 (90%) were tested for 2 disorders and 10 (10%) were tested for 3 disorders. Mutations for 12 genes were part of 3 or more mg-PGT-M, with FMR1 and BRCA the most common (Table). Thirty-nine cases were performed for 2 or more autosomal dominant (AD) conditions (AD/AD), 19 for AR/AR, 19 AD/AR, 12 XL/AR, 6 XL/AD and 1 XL/XL. There were no instances of cases with 3 inheritance patterns (i.e AR/AD/XL). In most mg-PGT-M cases, couples had mutations for the same gene. (0 common: 19, 1 common: 47, 2 common: 27, 3 common: 3). In the AD/AD cases that could be traced, 22/32 had positive family history and in 3 cases there were affected children. Of 13 AR/AR cases, 12 had an affected child. Of special interest is the cohort of AD/AD cases; in 12 cases, the patient carried both dominant disorders; in 9 the partner carried both disorders; and in 10 cases each partner carried 1 dominant disorder. It is of great interest that the largest number of mg-PGT-M cases is for 2 dominant genes. Since most of the AR/AR cases have been the result of having an affected child, this brings to the forefront the need for preconception genetic screening to be as wide as possible rather than risk having an affected child with a severe disease and in many cases an unfortunate demise