X-linked novel hemizygous ADGRG2 variants associated with male factor infertility.

ADGRG2

Hemizygous ADGRG2 variants (splicing, frameshift, nonsense, missense) leading to truncated proteins or reduced protein levels

To look for ADGRG2 variants in infertile men without an identified CFTR variant, the authors performed exome sequencing in 133 men with obstructive azoospermia. They identified eight pathogenic hemizygous ADGRG2 variants in nine unrelated patients with congenital bilateral absence of the vas deferens (CBAVD): one splice variant, three frameshifts, two nonsense variants (p.Arg825Ter, p.Glu991Ter) and two missense variants (p.Glu170Asp, p.Ser183Arg), all absent or rare in public databases. All carriers had azoospermia or severe oligozoospermia, and in vitro assays showed truncated proteins or reduced protein levels. Four patients treated with ICSI achieved fertilisation and pregnancy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

ADGRG2 should be systematically queried in the exome in CBAVD without a CFTR variant: X-linked inheritance changes genetic counselling, since all daughters conceived by ICSI will be carriers and no son will inherit the paternal variant. The series is small and the abstract does not report family segregation. The four pregnancies achieved with ICSI are a reassuring message for these couples.

Analysis by Dr Thibaut Benquey