nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/1680-4422-2017-2-246-254nid-367Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАнализ мутаций гена GNAS1 у пацинетов с хронической почечной недостаточностью, вторичным гиперпаратиреозом и обезображивающей деформацией лицевого скелета (синдромом Сагликера)Mutational analysis of the GNAS1 gene in patients with chronic renal failure, secondary hyperparathyroidism and uglifying face appearances (Sagliker syndrome)ОсманДемирханOsmanDemirhanosdemir@cu.edu.trЯхьяСагликерYahyaSaglikernoemail@neicon.ruЭлулАкбальEylulAkbalnoemail@neicon.ruМехметАли ЭркочMehmetAli Erkocnoemail@neicon.ruНурэйПайларNurayPaylarnoemail@neicon.ruДенизТастемирDenizTastemirnoemail@neicon.ruУниверситет Чукурова, Адана, ТурцияРоссияCukurova University, Adana-TurkiyeRussian FederationОтделение гипертензии и нефрологии Сагликера, Адана, ТурцияРоссияSagliker Hypertension and Nephrology Unit, Adana-TurkiyeRussian FederationПрофессиональная школа здравоохранения Университета Адиаман, Адиаман, ТурцияРоссияVocational Scool of Health Services, Adiyaman, TurkiyeRussian Federation201715082024192246254Copyright © Осман Д., Яхья С., Элул А., Мехмет А.Э., Нурэй П., Дениз Т., 20242024Осман Д., Яхья С., Элул А., Мехмет А.Э., Нурэй П., Дениз Т.Osman D., Yahya S., Eylul A., Mehmet A.E., Nuray P., Deniz T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/367

Синдром Сагликера (СС) ассоциирован с хронической болезнью почек (ХБП), вторичным гиперпаратиреозом (ВГПТ) и обезображиванием лицевого скелета. Этиология СС остается неустановленной, однако имеются серьезные основния полагать, что в его основе лежат генетические факторы. Значимость мутаций гена GNAS1 для исходов СС не вполне ясна, поиск мутаций GNAS1 с этой целью не проводился. Мы выполнили клиническое и генетическое обследование, включающее скрининг мутаций в 13 экзонах гена GNAS1 у 23 пациентов с СС. У 47,8% пацинетов было выявлено 17 генетических аномалий GNAS1. Семь (58,3%) из 12 нуклеотидных нарушений представляют собой новые миссенс-мутации, и три - нонсенс-мутации. Мутации носили разнородный характер. У 11 пацинетов выявлены миссенс- и нонсенс-мутации и гетерозиготные трансверсии (полиморфизмы) в 16 регионах гена GNAS1, тогда как в контрольной группе мутаций GNAS1 не обнаружено. Нонсенс-мутации обнаружены у 5 пацинетов. Полиморфизмы и другие непатогенные мутации найдены у 43,5% больных. Обнаружены также 6 гетерозиготных трансверсий в экзонах. Шесть представляли собой интронные мутации. Эти результаты расширяют спектр миссенс-мутаций гена GNAS1, ассоциированных с СС, и согласуются с представлениями о том, что недостаточность GNAS1 играет роль в формировании клинического фенотипа, причем основное значение имеют мутации, ведущие к полной потере функции за счет дефицита функциональной аллели GNAS1. Кроме того, полученные данные могут быть полезны для проведения дальнейших молекулярных и биологических исследований у больных с ХБП, вторичным гиперпаратиреозом и обезображиванием лицевого скелета.

Sagliker syndrome (SS) seems to be related to chronic kidney disease (CKD), secondary hyperparathyroidism (SH) and uglifying face appearances. The etiology of SS is not known, and it is strongly thought that genetics may be the major factor in the etiology. The genetics importance of GNAS1 gene mutations on outcome in patients with SS is unclear, and no search has addressed GNAS1 mutations. Therefore, we conducted clinical and genetical studies including screening for mutations in the 13 exons of the GNAS1 gene in 23 subjects with SS. In 47.8% of the patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and three nonsense. Mismutations were in different manners. For 16 regions of the GNAS1 gene in which a missense and nonsense mutations, and heterozigot transversions (polymorphisms) were identified in 11 patients, and no mutated GNAS1 genomic in DNA of control subjects. There was nonsense mutations in 5 patients. Polymorphisms and other nonpathogenic mutations have been identified in 43.5% of the patients. There were also 6 heterozygous tranversion polymorphism in exons. Six were introngenic mutations. These results expand the spectrum of GNAS1 missense mutations associated with SS, and are consistent with an insufficiency of GNAS1 playing a role in the clinical phenotype of loss of function mutations and with a functional GNAS1 allele having a predominant role. At the same time, these findings may be helpful in conducting further molecular and biological studies on CKD, secondary hyperparathyroidism and uglifying face appearances.

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The authors declare that there are no conflicts of interest present.