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dc.contributor.authorGüran, Tülay
dc.contributor.authorYeşil, Gözde
dc.contributor.authorTuran, Serap
dc.contributor.authorAtay, Zeynep
dc.contributor.authorBozkurtlar, Emine
dc.contributor.authorAghayev, AghaRza
dc.contributor.authorGül, Sinem
dc.contributor.authorTinay, İlker
dc.contributor.authorAru, Başak
dc.contributor.authorArslan, Sema
dc.contributor.authorKöroğlu, Mustafa Kutay
dc.contributor.authorErcan, Feriha
dc.contributor.authorYanıkkaya Demirel, Gülderen
dc.contributor.authorTanay Eren, Funda
dc.contributor.authorKarademir, Betül
dc.contributor.authorBereket, Abdullah
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:52:28Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:52:28Z
dc.date.issued2019en_US
dc.identifier.citationGüran, T., Yeşil, G., Turan, S., Atay, Z., Bozkurtlar, E., Aghayev, A. … Bereket, A. (2019). PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans. European Journal of Endocrinology, 180(5), 291-309. https://dx.doi.org/10.1530/EJE-19-0067en_US
dc.identifier.issn0804-4643
dc.identifier.issn1479-683X
dc.identifier.urihttps://dx.doi.org/10.1530/EJE-19-0067
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2407
dc.descriptionWOS: 000464997600005en_US
dc.descriptionPubMed ID: 30893644en_US
dc.description.abstractContext: Most of the knowledge on the factors involved in human sexual development stems from studies of rare cases with disorders of sex development. Here, we have described a novel 46, XY complete gonadal dysgenesis syndrome caused by homozygous variants in PPP2R3C gene. This gene encodes B '' gamma regulatory subunit of the protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase involved in the phospho-regulation processes of most mammalian cell types. PPP2R3C gene is most abundantly expressed in testis in humans, while its function was hitherto unknown. Patients and methods: Four girls from four unrelated families with 46, XY complete gonadal dysgenesis were studied using exome or Sanger sequencing of PPP2R3C gene. In total, four patients and their heterozygous parents were investigated for clinical, laboratory, immunohistochemical and molecular characteristics. Results: We have identified three different homozygous PPP2R3C variants, c.308T>C (pL103P), c.578T>C (pL193S) and c.1049T>C (pF350S), in four girls with 46, XY complete gonadal dysgenesis. Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay. We have shown a decreased SOX9-Phospho protein expression in the dysgenetic gonads of the patients with homozygous PPP2R3C variants suggesting impaired SOX9 signaling in the pathogenesis of gonadal dysgenesis. Heterozygous males presented with abnormal sperm morphology and impaired fertility. Conclusion: Our findings suggest that PPP2R3C protein is involved in the ontogeny of multiple organs, especially critical for testis development and spermatogenesis. PPPR3C provides insight into pathophysiology, as well as emerging as a potential therapeutic target for male infertility.en_US
dc.description.sponsorshipMedical Research Council of Marmara University [SAG-A-120418-0152]en_US
dc.description.sponsorshipThis work has been supported by the Medical Research Council of Marmara University (Project Grant SAG-A-120418-0152, T G).en_US
dc.language.isoengen_US
dc.publisherBioscientifica Ltden_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectTestisen_US
dc.subjectGonadsen_US
dc.subjectSex Reversalen_US
dc.titlePPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humansen_US
dc.typearticleen_US
dc.relation.journalEuropean Journal of Endocrinologyen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalıen_US
dc.authorid0000-0002-1044-6888en_US
dc.identifier.volume180en_US
dc.identifier.issue5en_US
dc.identifier.startpage291en_US
dc.identifier.endpage309en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1530/EJE-19-0067en_US


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