medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.03.35-46medgen-2277Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHНовая нонсенс-замена в гене CHD7 у пациента с синдромом CHARGE в ЯкутииA novel nonsense variant in the CHD7 gene in a patient with CHARGE syndrome in YakutiaКларовЛ. А.KlarovL. A.

677000, г. Якутск, ул. Ярославского, д. 6/3

677010, г. Якутск, Сергеляхское шоссе, д.4

6/3, Yaroslavskogo str., Yakutsk, 677000

4, Sergelyakhskoye Highway, Yakutsk, 677010

eizonix@gmail.comПшенниковаВ. Г.PshennikovaV. G.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3, Yaroslavskogo str., Yakutsk, 677000

ТерютинФ. М.TeryutinF. M.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3, Yaroslavskogo str., Yakutsk, 677000

ЛугиновН. В.LuginovN. V.

677010, г. Якутск, Сергеляхское шоссе, д.4

677000, г.Якутск, ул. Белинского, д. 58

4, Sergelyakhskoye Highway, Yakutsk, 677010

68, Belinsky str., Yakutsk, 677000

КотляровП. М.KotlyarovP. M.

117997, г. Москва, ул. Профсоюзная, д. 86

86, Profsoyuznaya str., Moscow, 117997

БарашковН. А.BarashkovN. A.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3, Yaroslavskogo str., Yakutsk, 677000

ФГБНУ «Якутский научный центр комплексных медицинских проблем»; ГАУ Республиканская больница №1 – Национальный центр медициныРоссияYakutsk Scientific Center for Complex Medical Problems; Republican Hospital No. 1 - National Center of MedicineRussian FederationФГБНУ «Якутский научный центр комплексных медицинских проблем»РоссияYakutsk Scientific Center for Complex Medical ProblemsRussian FederationГАУ Республиканская больница №1 – Национальный центр медицины; ФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова»РоссияRepublican Hospital No. 1 - National Center of Medicine; North-Eastern Federal University. M.K. AmmosovRussian FederationФГБУ «Российский научный центр рентгенорадиологии» Минздрава РоссииРоссияRussian Scientific Center for Radiology of the Ministry of Health of RussiaRussian Federation2023250720232233546Copyright © Кларов Л.А., Пшенникова В.Г., Терютин Ф.М., Лугинов Н.В., Котляров П.М., Барашков Н.А., 20232023Кларов Л.А., Пшенникова В.Г., Терютин Ф.М., Лугинов Н.В., Котляров П.М., Барашков Н.А.Klarov L.A., Pshennikova V.G., Teryutin F.M., Luginov N.V., Kotlyarov P.M., Barashkov N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2277

Синдром CHARGE – редкое аутосомно-доминантное заболевание, вызванное мутационными повреждениями в генах CHD7 и SEMA3E (OMIM 214800). Распространенность составляет примерно 1 случай на 12000 новорожденных. Большинство случаев синдрома CHARGE обусловлено de novo патогенными вариантами гена CHD7, кодирующего ДНК-связывающий белок хромодомена хеликазы 7, который ответственен за организацию хроматина. Аббревиатура «CHARGE» обобщает шесть клинических признаков синдрома: С (coloboma) – глазная колобома, H (heart defects) – пороки сердца, A (atresia of choanae) – атрезия хоан, R (retardation of growth) – задержка роста и / или развития, G (genital anomalies) – аномалии гениталий, E (ear abnormalities) – аномалии уха. В настоящей работе представлен клинический случай с ранее не описанной нонсенс заменой c.1940C>G (p.Ser647*) в гене CHD7, выявленной методом полноэкзомного секвенирования у пациента с недифференцированной формой потери слуха и множественными аномалиями развития. В результате клинико-генетического обследования у пациента выявлено 7 признаков, соответствующих обновленным диагностическим критериям синдрома CHARGE: три основных (аномалии внутреннего уха, глазная колобома и патогенные мутации в гене CHD7) и четыре второстепенных признака (задержка умственного развития, врожденный порок сердца, гипоталамо-гипофизарная дисфункция и дисфункция черепных нервов). В работе обсуждается связь с данным синдромом выявленных двух дополнительных признаков со стороны опорно-двигательного аппарата и эндокринной системы, не включенных в последнюю версию диагностических критериев синдрома CHARGE. Мы надеемся, что пристальное внимание к генотип-фенотипическим особенностям поможет определить, как лучше диагностировать, консультировать и оказывать необходимую медицинскую и социальную помощь пациентам с подобными редкими заболеваниями.

CHARGE syndrome is a rare autosomal dominant disease caused by mutational lesions in the CHD7 and SEMA3E genes (OMIM 214800). The prevalence is approximately 1 in 12,000 newborns. Most cases of CHARGE syndrome are caused by de novo pathogenic variants of the CHD7 gene, which encodes the DNA-binding protein helicase 7 chromodomain, which is responsible for chromatin organization. The abbreviation “CHARGE” summarizes six clinical signs of the syndrome: C - coloboma, H - heart defects, A - atresia of choanae, R - retardation of growth and/or development, G - genital anomalies, E - ear abnormalities. This paper presents a genotype-phenotypic analysis of a case with a previously unknown nonsense substitution c.1940C>G (p.Ser647*) in the CHD7 gene, identified by whole exome sequencing in a patient with an initially undifferentiated form of hearing loss associated with multiple developmental anomalies. As a result of a clinical examination, the patient revealed 7 signs that correspond to the updated diagnostic criteria for CHARGE syndrome: three main ones (anomalies of the inner ear, ocular coloboma and pathogenic variant in the CHD7 gene) and four secondary signs (mental retardation, congenital heart disease, cranial nerve dysfunction, hypothalamic-pituitary dysfunction). The paper discusses the relationship with this syndrome of the identified two additional signs from the endocrine system and the musculoskeletal system, not included in the latest version of the diagnostic criteria for the CHARGE syndrome. We hope that close attention to genotype-phenotypic characteristics will help determine how best to diagnose, counsel and provide the necessary medical and social care for patients with such rare diseases.

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