nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2018-22-2-74-80nefr-354Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSЯВЛЯЮТСЯ ЛИ МАМЫ МАЛЬЧИКОВ С БОЛЕЗНЬЮ ДЕНТА БЕССИМПТОМНЫМИ НОСИТЕЛЯМИ Х-СЦЕПЛЕННОЙ ТУБУЛОПАТИИ?ARE MOTHERS OF BOYS WITH DENT’S DISEASE ASYMPTOMATIC CARRIERS FOR X-LINKED TUBULAR DISORDER?ПриходинаЛ. С.PrikhodinaL. S.

Larisa S. Prikhodina, MD, PhD., DMedSci,Prof., Research Clinical Institute for Pediatrics n.a. acad. Y.E. Veltishev, Division of Inherited & Acquired Kidney Diseases 

125412 Moscow, Taldomskaya St., 2

prikhodina@rambler.ruПапижС. В.PapizhS. V.

Svetlana V. Papizh, MD, PhD. Research Clinical Institute for Pediatrics n.a. acad. Y.E. Veltishev, Division of Inherited & Acquired Kidney Diseases

125412 Moscow, Taldomskaya St., 2

papijsveta@mail.ruБашироваЗ. Р.BashirovaZ. R.

Баширова Зиля Рамилевна, Научно-исследовательский клинический институт педиатрии им. акад. Ю.Е. Вельтищева РНИМУ им. Н.И. Пирогова, отдел наследственных и приобретенных болезней почек

Zilya Bashirova,MD, Research Clinical Institute for Pediatrics n.a. acad. Y.E. Veltishev, Division of Inherited & Acquired Kidney Diseases 

125412 Moscow, Taldomskaya St., 2

z-bash@mail.ruЛюдвигМ.LudwigM.

Людвиг Михаэль, доктор медицинских наук, профессор, Молекулярно-биологическая лаборатория, отдел геномики

, 53127, г. Бонн, ул. Sigmund-Freud-Srabe, 25

Ludwig Michael, MD, PhD, Prof. Molecular Biology Laboratory, Department of GenomicsEndFragment 

53127 Bonn Sigmund-Freud-Srabe, 25

mludwig@uni-bonn.deРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова; Российская медицинская академия непрерывного профессионального образованияРоссияLarisa S. Prikhodina, MD, PhD., DMedSci,Russian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationИнститут клинической химии и фармакологииГерманияInstitute of Clinical Chemistry & Clinical PharmacologyGermany2018120220202227480Copyright © Приходина Л.С., Папиж С.В., Баширова З.Р., Людвиг М., 20202020Приходина Л.С., Папиж С.В., Баширова З.Р., Людвиг М.Prikhodina L.S., Papizh S.V., Bashirova Z.R., Ludwig M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/354

Болезнь Дента – Х-сцепленная проксимальная тубулопатия, характеризующаяся низкомолекулярной протеинурией, гиперкальциурией, нефрокальцинозом и прогрессированием в хроническую почечную недостаточность. Заболевание обусловлено мутациями в генах CLCN5 или OCRL и проявляется у лиц мужского пола, в то время как женщины являются бессимптомными носителями. ЦЕЛЬ: исследование фенотипа и генотипа матерей мальчиков с болезнью Дента для исключения бессимптомного носительства мутаций генов CLCN5 и OCRL, ответственных за развитие Х-сцепленной тубулопатии. ПАЦИЕНТЫ И МЕТОДЫ. Проведено клиническое и молекулярно-генетическое обследование 9 матерей 10 мальчиков с болезнью Дента из 8 неродственных семей. Прямое секвенирование по Сэнгеру генов CLCN5 и OCRL выполнено у всех пациентов и их мам. РЕЗУЛЬТАТЫ. Статус носителей болезни Дента 1-го (n=7) и 2-го (n=2) типов был подтвержден у всех обследованных мам пробандов. Превалирующими клиническими проявлениями болезни Дента у мам пациентов являлись снижение реабсорбции фосфатов, гипофосфатемия, медуллярный нефрокальциноз и прогрессирование в хроническую болезнь почек 2 стадии. Реже наблюдались низкомолекулярная протеинурия и гиперкальциурия. Полный фенотип болезни Дента выявлен у 2 женщин – двоюродных сестер, носителей болезни Дента 1-го типа. ЗАКЛЮЧЕНИЕ. У мам мальчиков с болезнью Дента установлена фенотипическая вариабельность клинических проявлений Х-сцепленной тубулопатии, что может быть следствием транслокации или инактивации Х-хромосомы. Полученные данные свидетельствуют о необходимости диагностического обследования матерей мальчиков с болезнью Дента с целью определения фенотипа и своевременной профилактики прогрессирования заболевания в хроническую почечную недостаточность.

Dent’s disease is an X-linked proximal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and progression to chronic kidney failure. The disease is caused by mutations in CLCN5 or OCRL genes and affects males, whereas female carriers are generally asymptomatic. THE AIM: to study phenotype and genotype of patients’ mothers with Dent’s disease to exclude asymptomatic carrier of CLCN5 or OCRL gene mutations responsible for X-linked tubulopathy development. PATIENTS AND METHODS. We conducted clinical and molecular-genetic study of 9 mothers of 10 boys with Dent’s disease from 8 unrelated families. Direct Sanger sequencing of CLCN5 and OCRL genes were carried out with genomic DNA of all patients and their mothers. RESULTS. Carrier status of Dent’s disease 1 (n=7) and 2 types (n=2) was confirmed in all patients’ mothers. The most prevalent features of Dent’s disease in probands’ mothers were decrease in phosphate reabsorption, hypophosphatemia, medullary nephrocalcinosis and progression to CKD 2 stage. Low molecular weight proteinuria and hypercalciuria were rare revealed in carrier females. Full phenotype of Dent’s disease discovered in 2 cousins females carrier for Dent’s disease 1 type. CONCLUSION. We found that all carrier females had phenotypic variation of Dent disease’ symptoms. We speculate that revealed phenotype in carrier females for Dent disease might be a consequence of autosome translocation or nonrandom X chromosome inactivation. These data suggest that clinicians should consider a diagnostic evaluation of mothers of boys with Dent’s disease to determine phenotype and early prevention of progression to chronic kidney disease.

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