A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT

Abstract

After four unsuccessful assisted reproductive techniques trials, a female was referred for genetic analysis. In this case study, we aimed to investigate the genetic etiology of a female withinfertility and oocyte maturation defect. Chromosome analysis and fluorescence in-situ hybridization (FISH) using X-centromeric (DXZ1) and SHOX-probe (SHOX/SE X) (CytoCell, Cambridge, UK) on interphase nuclei of lymphocytes and mucosal cells were performed. Exome sequencing using the Illumina platform and confirmatory studies, including intra-familial segregation analysis, was done by Sanger sequencing. Karyotyping and molecular cytogenetics studies were normal, and potential chromosomal abnormalities and mosaicism were excluded. WES data analysis identified a known, rare, nonsense pathogenic homozygous variant in exon 3 (NM_207341.4, c.628C>T; p.Q210*) of the ZP1 gene. Additionally, her parents, who were first-degree cousins, were heterozygotes for this variant. Zona pellucida is an essential glycoprotein that surrounds oocytes and contains four types of receptor proteins (ZP1-4). The detected mutation in the ZP1 gene leads to the premature stop codon, causing truncation of the ZP1 receptor protein. This is the first case report with ahomozygous variant associated with oocyte maturation defect. Also, exome sequencing is a valuable method to identify the genetic etiology in complex, multigenic conditions like infertility.

Keywords

• oomd
• zona pellucida
• zp1
• female infertility
• exome sequencing