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OOSİT MATÜRASYON DEFEKTİ OLAN BİR OLGUDA NADİR GÖRÜLEN ANLAMSIZ ZP1 VARYANTI

Yıl 2023, Cilt: 86 Sayı: 3, 264 - 267, 26.10.2023

Ezgi Gizem Berkay Birsen Karaman Oya Uyguner Seher Başaran

https://doi.org/10.26650/IUITFD.1303555

Öz

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.

Anahtar Kelimeler

OOMD zona pellusida ZP1 kadın infertilitesi ekzom dizileme

Destekleyen Kurum

İstanbul Üniversitesi BAP Birimi

Proje Numarası

TSA-2018-32135

Kaynakça

  • Beall S, Brenner C, Segars J. Oocyte maturation failure: a syndrome of bad eggs. Fertility and Sterility 2010;94(7):2507- 13. [CrossRef] google scholar
  • Huang HL, Lv C, Zhao YC, Li W, He XM, Li P, et al. Mutant ZP1 in familial infertility. N Engl J Med 2014;27;370(13):1220- 6. [CrossRef] google scholar
  • Yang P, Luan X, Peng Y, Chen T, Su S, Zhang C, et al. Novel zona pellucida gene variants identified in patients withoocyte anomalies. Fertility and Sterility 2017;107(6):1364-9. [CrossRef] google scholar
  • Zhou Z, Ni C, Wu L, Chen B, Xu Y, Zhang Z, et al. Novel mutations in ZP1, ZP2, and ZP3 cause female infertility due to abnormal zona pellucida formation. Hum Genet 2019;138(4):327-37. [CrossRef] google scholar
  • Yuan P, Li R, Li D, Zheng L, Ou S, Zhao H, et al. Novel mutation in the ZP1 gene and clinical implications. J Assist Reprod Genet 2019;36(4):741-7. [CrossRef] google scholar
  • Dai C, Chen Y, Hu L, Du J, Gong F, Dai J, et al. ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report. Human Reproduction. 2019;34(11):2201-7 [CrossRef] google scholar
  • Sun L, Fang X, Chen Z, Zhang H, Zhang Z, Zhou P, et al. Compound heterozygous ZP1 mutations cause empty follicle syndrome in infertile sisters. Human Mutation 2019;40(11):2001-6. [CrossRef] google scholar
  • Okutman Ö, Demirel C, Tülek F, Pfister V, Büyük U, Muller J, et al. Homozygous splice site mutation in ZP1 causes familial oocyte maturation defect. Genes 2020;11(4):382. [CrossRef] google scholar
  • Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet google scholar

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

Yıl 2023, Cilt: 86 Sayı: 3, 264 - 267, 26.10.2023

Ezgi Gizem Berkay Birsen Karaman Oya Uyguner Seher Başaran

https://doi.org/10.26650/IUITFD.1303555

Öz

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.

Anahtar Kelimeler

OOMD zona pellucida ZP1 female infertility exome sequencing

Proje Numarası

TSA-2018-32135

Kaynakça

  • Beall S, Brenner C, Segars J. Oocyte maturation failure: a syndrome of bad eggs. Fertility and Sterility 2010;94(7):2507- 13. [CrossRef] google scholar
  • Huang HL, Lv C, Zhao YC, Li W, He XM, Li P, et al. Mutant ZP1 in familial infertility. N Engl J Med 2014;27;370(13):1220- 6. [CrossRef] google scholar
  • Yang P, Luan X, Peng Y, Chen T, Su S, Zhang C, et al. Novel zona pellucida gene variants identified in patients withoocyte anomalies. Fertility and Sterility 2017;107(6):1364-9. [CrossRef] google scholar
  • Zhou Z, Ni C, Wu L, Chen B, Xu Y, Zhang Z, et al. Novel mutations in ZP1, ZP2, and ZP3 cause female infertility due to abnormal zona pellucida formation. Hum Genet 2019;138(4):327-37. [CrossRef] google scholar
  • Yuan P, Li R, Li D, Zheng L, Ou S, Zhao H, et al. Novel mutation in the ZP1 gene and clinical implications. J Assist Reprod Genet 2019;36(4):741-7. [CrossRef] google scholar
  • Dai C, Chen Y, Hu L, Du J, Gong F, Dai J, et al. ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report. Human Reproduction. 2019;34(11):2201-7 [CrossRef] google scholar
  • Sun L, Fang X, Chen Z, Zhang H, Zhang Z, Zhou P, et al. Compound heterozygous ZP1 mutations cause empty follicle syndrome in infertile sisters. Human Mutation 2019;40(11):2001-6. [CrossRef] google scholar
  • Okutman Ö, Demirel C, Tülek F, Pfister V, Büyük U, Muller J, et al. Homozygous splice site mutation in ZP1 causes familial oocyte maturation defect. Genes 2020;11(4):382. [CrossRef] google scholar
  • Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet google scholar
Toplam 9 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Hizmetleri ve Sistemleri (Diğer)
Bölüm Olgu Sunumu
Yazarlar

Ezgi Gizem Berkay 0000-0002-1967-705X

Birsen Karaman 0000-0001-8640-0176

Oya Uyguner 0000-0002-2035-4338

Seher Başaran 0000-0001-8668-4746

Proje Numarası TSA-2018-32135
Yayımlanma Tarihi 26 Ekim 2023
Gönderilme Tarihi 27 Mayıs 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 86 Sayı: 3

Kaynak Göster

APA Berkay, E. G., Karaman, B., Uyguner, O., Başaran, S. (2023). A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT. Journal of Istanbul Faculty of Medicine, 86(3), 264-267. https://doi.org/10.26650/IUITFD.1303555
AMA Berkay EG, Karaman B, Uyguner O, Başaran S. A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT. İst Tıp Fak Derg. Ekim 2023;86(3):264-267. doi:10.26650/IUITFD.1303555
Chicago Berkay, Ezgi Gizem, Birsen Karaman, Oya Uyguner, ve Seher Başaran. “A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT”. Journal of Istanbul Faculty of Medicine 86, sy. 3 (Ekim 2023): 264-67. https://doi.org/10.26650/IUITFD.1303555.
EndNote Berkay EG, Karaman B, Uyguner O, Başaran S (01 Ekim 2023) A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT. Journal of Istanbul Faculty of Medicine 86 3 264–267.
IEEE E. G. Berkay, B. Karaman, O. Uyguner, ve S. Başaran, “A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT”, İst Tıp Fak Derg, c. 86, sy. 3, ss. 264–267, 2023, doi: 10.26650/IUITFD.1303555.
ISNAD Berkay, Ezgi Gizem vd. “A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT”. Journal of Istanbul Faculty of Medicine 86/3 (Ekim 2023), 264-267. https://doi.org/10.26650/IUITFD.1303555.
JAMA Berkay EG, Karaman B, Uyguner O, Başaran S. A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT. İst Tıp Fak Derg. 2023;86:264–267.
MLA Berkay, Ezgi Gizem vd. “A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT”. Journal of Istanbul Faculty of Medicine, c. 86, sy. 3, 2023, ss. 264-7, doi:10.26650/IUITFD.1303555.
Vancouver Berkay EG, Karaman B, Uyguner O, Başaran S. A CASE REPORT OF A RARE NONSENSE ZP1 VARIANT IN A PATIENT WITH OOCYTE MATURATION DEFECT. İst Tıp Fak Derg. 2023;86(3):264-7.
 Kapak Resmi İndir

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