分子遺伝医学

Three Male Siblings Undergoing Multiple IVF Failures Where a PLCZ1 Mutation Finally Revealed After a WES Analysis. A Three Couple’s Odyssey due to a Genetic Cause Ended Using Donor Sperm Eventually: A Family Case Report

Abstract

Maria Galiotou1*, Robert Najdecki1, Georgios Michos2, Foteini Chouliar1, Tatiana Chartomatsidou1, Kakani Ourania1, Nikos Peitsidis1, Evi Timotheo1, Christopikou Dimitra1 and Evaggelos Papanikolaou1,2

We present a case involving three brothers, all experiencing either normo- or oligospermia, who underwent several In-Vitro Fertilization (IVF) procedures without achieving a successful live birth. Each couple struggled with male or unexplained primary infertility for 10-15 years. Upon genetic testing, the second brother underwent Whole Exome Sequencing (WES), which revealed a mutation in the phospholipase C zeta 1 (PLCζ1) gene. This discovery introduced a new dimension to their infertility struggle, shedding light on the underlying issue hindering their ability to conceive.

The PLCζ1 gene, situated on chromosome 12, governs the production of the PLCζ1 enzyme. This enzyme primarily operates within the head of spermatozoa, playing a crucial role in regulating calcium signaling during fertilization. PLCζ1 facilitates the generation of inositol trisphosphate (IP3) within sperm cells, initiating a cascade of calcium ion (Ca²⁺) release events vital for fertilization, including egg activation and the fusion of sperm and egg nuclei.

With the knowledge of their genetic condition, all three brothers opted for the use of donor sperm. Consequently, two of them have since become parents, while the third is currently undergoing a pregnancy. This case underlies the importance of WES analysis in diagnosing cases of prolonged male and/or female infertility and repeated IVF failures.