A homozygous FANCM frameshift pathogenic variant causes male infertility

摘要

Purpose: Fanconi anemia (FA) genes play important roles in spermatogenesis. In mice, disruption of Fancm impairs male fertility and testicular integrity, but whether FANCM pathogenic variants (PV) similarly affect fertility in men is unknown. Here we characterize a Pakistani family having three infertile brothers, two manifesting oligoasthenospermia and one exhibiting azoospermia, born to first-cousin parents. A homozygous PV in FANCM (c. 1946_1958del, p. P648Lfs*16) was found cosegregating with male infertility. Our objective is to validate that FANCM p. P648Lfs*16 is the PV causing infertility in this family.