A case report of a rare nonsense ZP1 variant in a patient with oocyte maturation defect

Berkay E. G., Karaman B., Toksoy G., Özsait Selçuk B. Ş., Uyguner Z. O., Başaran S.

ESHG 2020, 6 - 09 June 2020, pp.1

  • Publication Type: Conference Paper / Summary Text
  • Page Numbers: pp.1
  • Istanbul University Affiliated: Yes


Introduction: Oocyte maturation defect (OOMD) is a rare condition causing female infertility that can be diagnosed during assisted reproduction techniques (ART). OOMD related genes are ZP1, ZP2, ZP3, PANX1, PATL2, TUBB8, WEE2 (OMIM, 2020). We report a case of a 31-year-old woman who had four ART failures diagnosed as empty follicle syndrome and OOMD. She has short stature (-3 SD), bilateral limited extension-exion on elbows. Materials and Methods: Chromosome analysis and uorescence in-situ hybridization (FISH) using X chromosome centromeric and SHOX-probe on interphase nuclei of lymphocytes and mucosal cells was investigated. Whole-exome sequencing (WES) performed via the Illumina platform. Conrmation and familial segregation analysis were performed by Sanger sequencing. Results: Karyotyping and FISH resulted in normal, possible mosaicism was excluded. WES analysis revealed a known, rare, pathogenic homozygous variant in exon 3 (c.628C>T; p.Q210*) of ZP1 gene, and her parents being rst degree cousins were carriers for this variant. Conclusions: ZP1 with autosomal recessive inheritance is related to OOMD-1 (MIM_615774). Zona pellucida (ZP) is a glycoprotein structure surrounding oocytes and is essential for oocyte development. ZP contains four types of receptor proteins (ZP1-4). Our variant in ZP1 is nonsense, premature stop codon causes to truncate ZP1 receptor proteins. This is the rst homozygous occurrence of this variant associated with OOMD. WES ndings were also analyzed for known genes related to short stature and no pathogenic variant has been observed. WES is a valuable method to identify the genetic origin in complex, multigenic conditions like in infertility.Istanbul University ProjectNumber:TSA-2018-32135