OOSİT MATÜRASYON DEFEKTİ OLAN BİR OLGUDA NADİR GÖRÜLEN ANLAMSIZ ZP1 VARYANTI

Abstract

Bu çalışmada yardımcı üreme tedavisi sonrasında dört başarısız denemesi olan kadın bir olguda, infertilite ve oosit olgunlaşma bozukluğunun genetik etiyolojisinin araştırılması amaçlanmıştır. Lenfositlerin ve mukozal hücrelerin interfaz çekirdekleri üzerinde X-sentromerik (DXZ1) ve SHOX-probu (SHOX/SE X) (CytoCell, Cambridge, UK) kullanılarak kromozom analizi ve floresans hibridizasyonu (FISH) yapıldı. Ekzom dizilemede Illumina platformu; bulunan varyantın doğrulaması ve aile içi segregasyon analizi için Sanger dizileme tekniği ullanıldı. Karyotip ve moleküler sitogenetik analiz sonuçları normaldi, potansiyel kromozomal anomaliler ve mozaiklik dışlandı. Tüm ekzom veri analizinde, ZP1 geni 3. ekzonunda (NM_207341.4, c.628C>T; p.Q210*) bilinen, nadir, anlamsız bir patojenik homozigot varyant tanımladı. Segregasyon çalışmasında birinci derece kuzen olan ebeveynlerinin bu varyant için heterozigot oldukları bulundu. Erken durdurma kodonu bileşimindeki bu mutasyon, ZP1 reseptör proteininin kısa sentezlenmesine neden olmaktadır. Zona pellusida, oositleri çevreleyen ve dört tip reseptör proteini (ZP1-4) içeren temel bir glikoproteindir. Bu çalışma, tespit edilen homozigot varyantın oosit matürasyon defekti ve kadın infertilitesi ile ilişkili olduğunu gösteren ilk olgu sunumudur. Ayrıca, ekzom dizileme yönteminin infertilite gibi karmaşık, multigenik durumlarda genetik etiyolojiyi belirlemek için kullanılabilecek değerli bir yöntem olduğu görülmüştür.

Keywords

• OOMD
• zona pellusida
• ZP1
• kadın infertilitesi
• ekzom dizileme

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 with infertility 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 a homozygous 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

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