Novel zona pellucida gene variants identified in patients with oocyte anomalies.

OBJECTIVE: To detect ZP (zona pellucida) gene (ZP1-ZP4) mutations in patients with oocyte anomalies.

DESIGN: Case-control genetic study.

SETTING: University-based reproductive medicine center.

PATIENT(S): A total of 92 infertile patients with repeated cycles of oocyte maturation arrest (group I, n = 49) or oocyte morphologic defect (group II, n = 43) as well as 373 healthy controls.

INTERVENTION(S): Genomic DNA extracted from peripheral blood and coding regions of ZP genes amplified by polymerase chain reaction and sequenced by a DNA analyzer.

MAIN OUTCOME MEASURE(S): Variant prediction of ZP genes with software.

RESULT(S): In group I with oocyte maturation arrest, no novel variants were found. In group II with oocyte morphologic defects, four novel variants, two in the ZP1 gene [c.247T>C (p.W83R) and c.1413G>A (p.W471X)] and two in the ZP2 gene [c.1599G>T (p.R533S) and c.1696T>C (p.C566R)] were detected in 4 of 43 patients (approximately 9%) but were absent from the controls. Protein alignments showed that the four variants were highly conserved among different species, and all four variants were predicted to be deleterious by gene software predictions.

CONCLUSION(S): ZP gene variants may account for patients with oocyte morphologic abnormalities but not for those with oocyte maturation arrest.