A novel homozygous DLGAP5 splice-site variant in a woman with oocyte maturation arrest and recurrent IVF failure: a case report
TL;DR
A 27-year-old Asian - Indian woman from a consanguineous family with 5 years of primary infertility and two IVF cycles characterized by poor metaphase II oocyte yield and complete blastocyst arrest is reported, highlighting the value of genomic testing in women with recurrent IVF failure and an OMA-like embryology phenotype.
Abstract
Oocyte maturation arrest (OMA) is a rare cause of female infertility characterized by impaired oocyte maturation and recurrent failure of assisted reproductive technologies. Recent studies have identified DLGAP5 as a critical regulator of meiotic spindle assembly, with biallelic variants causing oocyte maturation defects and early embryonic arrest. Till date, 10 females from seven families have been reported. We report a 27-year-old Asian - Indian woman from a consanguineous family with 5 years of primary infertility and two IVF cycles characterized by poor metaphase II (MII) oocyte yield and complete blastocyst arrest. Whole-exome sequencing identified a novel canonical splice-acceptor variant, c.2064-1G>A, in homozygous state in DLGAP5. Segregation analysis confirmed heterozygous carrier status in both parents, whereas the variant was absent from the apparently healthy male sibling. This report expands the mutational spectrum of DLGAP5 and highlights the value of genomic testing in women with recurrent IVF failure and an OMA-like embryology phenotype.