ASTL is mutated in female infertility

Hum Genet. 2022 Jan;141(1):49-54. doi: 10.1007/s00439-021-02388-8.

Sateesh Maddirevula ^# ¹, Serdar Coskun ^# ², Mashael Al-Qahtani ¹, Omar Aboyousef ¹, Saad Alhassan ³, Meshael Aldeery ³, Fowzan S Alkuraya ⁴ ⁵

Affiliations

1 Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.
2 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center and College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
3 Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
4 Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia. falkuraya@kfshrc.edu.sa.
5 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia. falkuraya@kfshrc.edu.sa.
# Contributed equally.

PMID: 34704130 DOI: 10.1007/s00439-021-02388-8

Abstract

Female infertility is a relatively common phenotype with a growing number of single gene causes although these account for only a minority of cases. Here, we report a consanguineous family in which adult females who are homozygous for a truncating variant in ASTL display markedly reduced fertility in a pattern strikingly similar to Astl^-/- female mice. ASTL encodes ovastacin, which is known to trigger zona pellucida hardening (ZPH) as part of the cortical reaction upon fertilization. ZPH is required for normal early embryonic development and its absence can be caused by pathogenic variants in Other zona pellucida proteins that result in a similar infertility phenotype in humans and mouse. This is the first report of ASTL-related infertility in humans and suggests that the inclusion of ASTL in female infertility gene panels is warranted.

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