nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/2618-9801-2023-1-102-110nid-106Research ArticleШКОЛА НЕФРОЛОГАEDUCATIONAL MATERIALSПатология почек при синдроме Таунс-Брокса. Литературный обзор и клиническое наблюдениеKidney involvement in the Townes-Brocks syndrome. Literature review and clinical observationХохловаА. М.KhokhlovaA. M.ann.kechina@gmail.comОбуховаВ. А.ObukhovaV. A.obuhova.v@mail.ruДлинВ. В.DlinV. V.vdlin@pedklin.ruФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияPirogov Russian National Research Medical UniversityRussian Federation202321062024251102110Copyright © Хохлова А.М., Обухова В.А., Длин В.В., 20242024Хохлова А.М., Обухова В.А., Длин В.В.Khokhlova A.M., Obukhova V.A., Dlin V.V.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/106

Синдром Таунс-Брокса (ТБС) (OMIM #107480) - редкое аутосомно-доминантное заболевание, ассоциированное с мутацией в гене SALL1. ТБС характеризуется вариабельным сочетанием врожденных пороков развития, основными из которых являются аномалии аноректальной области, большого пальца кисти и наружного уха. Учитывая ключевую роль, которую SALL1 играет в нефрогенезе в качестве фактора транскрипции, аномалии развития почек и мочевыводящих путей (CAKUT) также могут встречаться у пациентов с ТБС. Они относятся к дополнительным критериям синдрома наряду с тугоухостью, врожденными пороками развития стоп, глаз и сердечно-сосудистой системы. В данной статье мы приводим клиническое наблюдение девочки с патологией почек в рамках ТБС при отсутствии полноценной триады признаков. У нее присутствовал лишь один большой критерий (добавочная дистальная фаланга большого пальца кисти), два малых критерия (двустороння гипоплазия почек и дефект строения переднего листка радужки) и признаки тубулярной дисфункции (низкомолекулярная протеинурия, глюкозурия). Отмечалось также снижение фильтрационной функции почек до ХБП С3а (рСКФ=52 мл/мин/1,73 м2). При проведении полноэкзомного секвенирования у девочки был выявлен не описанный ранее в литературе вариант в гене SALL1 (chr16:51175421G>A) с.712С>T (p.Gln238Ter) в гетерозиготном состоянии, который был валидирован секвенированием по Сэнгеру, что позволило подтвердить диагноз ТБС. Тот же вариант в гене SALL1 (chr16:51175421G>A) был в последующем идентифицирован у матери в сочетании с клиническими проявлениями синдрома в виде двусторонней гипоплазии почек со снижением фильтрационной функции (рСКФ=40,3 мл/мин/1,73 м2), что позволяет говорить о семейном случае ТБС.

Townes-Brocks syndrome (TBS, OMIM #107480) is a rare disease with autosomal dominant inheritance caused by pathogenic variants in the SALL1 gene. TBS is characterized by a variable combination of congenital anomalies, the major of which are imperforate anus, dysplastic ears, and thumb malformations. Due to the essential role of SALL1 in kidney development as a transcription factor, congenital anomalies of the kidney and urinary tract (CAKUT) could be also observed in patients with TBS. They belong to the minor signs of the syndrome, such as hearing loss, foot malformations, ocular features, and congenital heart disease. In this article, we present a clinical observation of a child with renal involvement as an exhibition of TBS with the absence of the full classical triad. The child had only one (bifid thumb) out of 3 major features, 2 minor signs (bilateral kidney hypoplasia, iris defect), and tubular dysfunction (low-molecular proteinuria, glucosuria). Progression to CKD grade 3а (eGFR 52 ml/min/1.73 m2) in the index case was remarkable. The whole exome sequencing identified a novel heterozygous nonsense variant (chr16:51175421G>A) с.712С>T (p.Gln238Ter) in the SALL1 gene, which was validated by Sanger sequencing, and diagnosis of TBS was confirmed. The same SALL1 variant (chr16:51175421G>A) was identified in her mother with a combination of clinical futures of the syndrome, such as bilateral kidney hypoplasia with decreased glomerular filtration (eGFR 40.3 ml/min/1.73 m2), that suggested a familiar case of TBS.

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