problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13565problendo-13565Research ArticleДетская эндокринологияPediatric EndocrinologyПолиморфизм синдрома Каллера-ДжонсаCuller-Jones syndrome polymorphismhttps://orcid.org/0009-0005-7797-5919РайкинаЕ. Н.RaykinaE. N.

Райкина Елизавета Николаевна 

117036, Москва, ул. Дм. Ульянова, д. 11

Elizaveta N. Raykina, MD

11 Dm. Ulyanova street, 117036 Moscow

dr.raykina@mail.ruhttps://orcid.org/0000-0001-7736-5372КолодкинаА. А.KolodkinaA. A.

Колодкина Анна Александровна, к.м.н. 

Москва

Anna A. Kolodkina, MD, PhD

Moscow

anna_kolodkina@mail.ruhttps://orcid.org/0000-0003-3127-5974БолмасоваА. В.BolmasovaA. V.

Болмасова Анна Викторовна, к.м.н. 

Москва

Anna V. Bolmasova

Moscow

bolmasova.anna@endocrincentr.ruhttps://orcid.org/0000-0003-0259-372XБондаренкоС. П.BondarenkoS. P.

Бондаренко София Павловна

Москва

Sofiia P. Bondarenko

Moscow

sofiyabondrnimu@gmail.comhttps://orcid.org/0000-0003-3396-8678ПанкратоваМ. С.PankratovaM. S.

Панкратова Мария Станиславовна, к.м.н. 

Москва

Maria S. Pankratova, MD, PhD

Moscow

ms_pankratova@mail.ruhttps://orcid.org/0000-0001-8500-4841ТюльпаковА. Н.TiulpakovA. N.

Тюльпаков Анатолий Николаевич, д.м.н. 

Москва

Anatoliy N. Tyulpakov, MD, PhD

Moscow

ant@endocrincentr.ruhttps://orcid.org/0000-0003-1290-574XЗабудскаяК. Г.ZabudskayaK. G.

Забудская Ксения Геннадьевна

Москва

Ksenya G. Zabudskaya

Moscow

zabudskaya.kseniya@endocrincentr.ruhttps://orcid.org/0000-0001-9621-5732БезлепкинаО. Б.BezlepkinaO. B.

Безлепкина Ольга Борисовна, д.м.н., профессор 

Москва

Olga B. Bezlepkina, MD, PhD, Professor

Moscow

olga.bezlepkina@endocrincentr.ruНациональный медицинский исследовательский центр эндокринологии им. акад. И.И. ДедоваРоссияEndocrinology Research CentreRussian FederationМедико-генетический научный центр имени академика Н.П. Бочкова; Российская детская клиническая больница ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияResearch Centre for Medical Genetics; Russian Children’s Clinical HospitalRussian Federation2025021220257155867Copyright © Райкина Е.Н., Колодкина А.А., Болмасова А.В., Бондаренко С.П., Панкратова М.С., Тюльпаков А.Н., Забудская К.Г., Безлепкина О.Б., 20252025Райкина Е.Н., Колодкина А.А., Болмасова А.В., Бондаренко С.П., Панкратова М.С., Тюльпаков А.Н., Забудская К.Г., Безлепкина О.Б.Raykina E.N., Kolodkina A.A., Bolmasova A.V., Bondarenko S.P., Pankratova M.S., Tiulpakov A.N., Zabudskaya K.G., Bezlepkina O.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13565ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Синдром Каллера-Джонса — редкое аутосомно-доминантное заболевание, причиной которого являются изменения нуклеотидной последовательности в гене GLI2. Распространенность данной патологии неизвестна, так как число наблюдений невелико, у части носителей вариантов в гене GLI2 проявления заболевания отсутствуют. Клинический фенотип заболевания гетерогенен и включает в себя гипопитуитаризм, пороки развития внутренних органов, лицевые дисморфизмы, полидактилию. С момента открытия гена GLI2 Roеssler Е. и соавт. в 2003 г. спектр клинических проявлений, а также понимание патогенеза развития компонентов заболевания значительно расширились. Для гена GLI2 описана неполная пенетрантность, клинический фенотип заболевания различается даже у членов одной семьи с одним и тем же нуклеотидным вариантом.

ЦЕЛЬ

ЦЕЛЬ. Изучение клинического и молекулярно-генетического полиморфизма у пациентов с синдромом Каллера-Джонса.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Проведено одноцентровое неинтервенционное одномоментное несравнительное исследование. Обследованы дети с синдромом Каллера-Джонса с подтвержденной генетической причиной заболевания. Всем пациентам проведено комплексное обследование, включая лабораторно-инструментальные методы диагностики и секвенирование панели генов «Гипопитуитаризм» методом NGS (next-generation sequencing).

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. В исследование включены 18 детей (7 девочек; 11 мальчиков) с вариантными заменами в гене GLI2. Возраст на момент обследования составил 8,95 года [4,6; 12,4]. Соматотропная недостаточность установлена у всех детей, возраст диагностики — 2 года [1; 6,5]. Вторичный гипотиреоз диагностирован 13 детям в возрасте 1,5 года [1; 3.5]. Уровень свободного тироксина на момент диагностики — 8,9 пмоль/л [7,5; 11,3]. Вторичный гипокортицизм установлен 10 детям в возрасте 2 лет [1,5; 2,8], уровень кортизола на момент диагностики — 84 нмоль/л [47; 152]. Характерные для синдрома внегипофизарные проявления выявлены у половины пациентов и включают в себя аномалии челюстно-лицевой области, пороки развития сердечно-сосудистой, мочевыделительной систем, а также пороки развития глаз. Полидактилия выявлена у двух детей.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Проведенное исследование демонстрирует клинический полиморфизм синдрома Каллера-Джонса, а также отсутствие корреляции «генотип-фенотип» для данного заболевания.

BACKGROUND

BACKGROUND: Culler-Jones syndrome is a rare autosomal dominant disease caused by nucleotide sequence changes in the GLI2 gene. The prevalence of this pathology is unknown, as the number of observations is small, some carriers of variants in the GLI2 gene have no manifestations of the disease. The clinical phenotype of the disease is heterogeneous and includes hypopituitarism, malformations of internal organs, facial dysmorphisms, and polydactyly. Since the discovery of the GLI2 gene by Roessler E. et al. in 2003, the spectrum of clinical manifestations, as well as the understanding of the pathogenesis of the disease components, has expanded considerably. Incomplete penetrance has been described for the GLI2 gene, and the clinical phenotype of the disease differs even among members of the same family with the same nucleotide variant.

AIM

AIM: Study clinical and molecular genetic polymorphism in patients with Culler-Jones syndrome.

MATERIALS AND METHODS

MATERIALS AND METHODS: A single-center, non-interventional, single-stage, non-comparative study was conducted. Children with Culler-Jones syndrome with a confirmed genetic cause of the disease were examined. All patients underwent a comprehensive examination, including laboratory and instrumental diagnostic methods and sequencing (by NGS (next-generation sequencing).

RESULTS

RESULTS: 18 children (7 girls; 11 boys) with variants in the GLI2 gene were included in the study. The age at the time of examination was 8.95 years [4,6; 12.4]. Growth hormone deficiency was noted in all children at age of 2 years [1; 6,5]. Central hypothyroidism was diagnosed in 13 children at the age of 1.5 years [1; 3.5]. Free thyroxine level at the time of diagnosis was 8.9 pmol/L [7.5; 11.3]. Secondary hypoadrenocorticism was diagnosed in 10 children at the age of 2 years [1.5; 2.8], with a cortisol level of 84 nmol/L at the time of diagnosis [47; 152]. Extrahypophyseal manifestations characteristic of the syndrome were detected in half of the patients and included maxillofacial anomalies, malformations of the cardiovascular and urinary systems and eye malformations. Polydactyly was detected in two children.

CONCLUSION

CONCLUSION: The present study demonstrates the clinical polymorphism of Culler-Jones syndrome and the lack of genotype-phenotype correlation for this disease.

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