PGT-M FOR AUTOSOMAL RECESSIVE CARRIERS OF CONDITIONS WITH AN AUTOSOMAL DOMINANT CANCER RISK: A CALL FOR ACTION

Abstract

To investigate the prevalence and indication of PGT-M cases performed for carriers of autosomal recessive (AR) conditions associated with an autosomal dominant (AD) cancer predisposition. All patients from 2018-2021 with a PGT-M test prepared for either an AR or AD inheritance (for cancer risk) were included in the study. Genes evaluated included: PALB2, BRIP2, ATM, MLH1, MSH2, MSH6, PMS2, FH, FANCA, FANCC, and RECQL3. The number of PGT-M cases prepared for each condition was identified as well as whether the intention for PGT-M was for the AR or AD pattern. In our study period, more than 4000 PGT-M cases were prepared of which 114 cases were performed for the genes selected. Of these, 101 (88.6%) were performed for the AD cancer predisposition and 13 (11.4%) for AR inheritance pattern. The genes tested most for AD included: MSH2, (25/101), MLH1 (19/101) and MSH6 (18/101). The genes tested most for their AR pattern were FANCA (6/13) and ATM (3/13) (Table). As expanded carrier screening and genetic panel testing increase in frequency, a large number of patients are utilizing PGT-M for conditions associated with AD cancer risk caused by genes historically known for their involvement in AR disorders. This phenotypic duality is often times not appreciated by clinicians and is often overlooked, therefore leaving the offspring at a risk for developing cancer.