Pathogenic variants in GALNT3, GALNT8, and GALNTL5 are associated with distinct sperm defects in human asthenoteratozoospermia.

GALNT3, GALNT8, GALNTL5

Variants in GALNT3 (acrosome), GALNT8 (flagellum) and GALNTL5 (head and flagellum), with markedly reduced or absent protein expression

This case-control study in a Southwest Chinese population compares 1148 men with asthenoteratozoospermia and 678 fertile controls by exome sequencing, focusing on the GALNT gene family. Infertile men carried significantly more GALNT variants per individual, and potentially deleterious variants were found only in them. GALNT3 variants were associated with globozoospermia, GALNT8 variants with severe flagellar abnormalities with loss of the central microtubule pair, and GALNTL5 variants with combined head and tail defects, with markedly reduced or absent mutant protein expression. ICSI outcomes in carriers were comparable to those of controls.

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

The gene–sperm phenotype correspondences are clear and helpful for guiding exome interpretation in male infertility, especially in globozoospermia. But the abstract gives neither the number of carriers per gene, nor the inheritance mode, nor the details of ACMG classification: the real weight of each gene remains to be quantified and replicated outside this population. The reassuring message on ICSI is valuable for reproductive counselling.

Analysis by Dr Thibaut Benquey