vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-37vavilov-4146Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSПолное секвенирование экзома позволило безошибочно диагностировать синдром Франка–Тер Хаара в одной из саудоаравийских семейWhole exome sequencing enables the correct diagnosis of Frank–Ter Haar syndrome in a Saudi familyХанЯ. Н.KhanY. N.ynkhanlughmani@gmail.comМахмудМ. Имад А.М.MahmudM. Imad A.M.ОтманН.OthmanN.РандзуанХ. М.RadzuanH. M.БаситС.BasitS.

Медина

Al Madinah Al Munawara

Кафедра фундаментальных медицинских наук, медицинский факультет, Международный исламский университет МалайзииМалайзияDepartment of Basic Medical Sciences, Faculty of Medicine, International Islamic University MalaysiaMalaysiaКафедра биохимии и молекулярной медицины, медицинский колледж, Университет Тайба; Центр генетики и наследственных заболеваний, Университет ТайбаСаудовская АравияDepartment of Biochemistry and Molecular Medicine, College of Medicine, Taibah University; Center for Genetics and Inherited Diseases, Taibah UniversitySaudi Arabia202430052024283326331Copyright © Хан Я.Н., Махмуд М., Отман Н., Рандзуан Х.М., Басит С., 20242024Хан Я.Н., Махмуд М., Отман Н., Рандзуан Х.М., Басит С.Khan Y.N., Mahmud M., Othman N., Radzuan H.M., Basit S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4146

Синдром Франка–Тер Хаара (Frank–Ter Haar syndrome, FTHS) – редкое генетическое заболевание с аутосомно-рецессивным типом наследования, характеризующееся аномалиями развития сердечно-сосудистой системы, костей лицевого черепа и скелета. Наиболее распространенной причиной развития данного синдрома являются мутации в гене SH3PXD2B. Для исследования была выбрана семья, в которой двое детей (трехлетняя девочка и двухмесячный мальчик) страдали двусторонней косолапостью. В семейной родословной указывался аутосомно-рецессивный тип наследования. Из крови шести членов семьи мы выделили образцы ДНК. Для упомянутых двоих детей было проведено полное секвенирование экзома, а секвенированием по Сэнгеру подтверждено наличие мутантного варианта у всех членов семьи. По результатам анализа данных полноэкзомного секвенирования (WES) была выявлена редкая гомозиготная мутация (c.280C>G; p.R94G) в гене SH3PXD2B. Секвенирование по Сэнгеру показало, что эта мутация идеально сегрегирует с указанным фенотипом в родословной. Более того, при использовании ряда инструментальных средств получены данные, предсказывающие вредность и опасность этой мутации. При повторном посещении членов семьи с целью проведения развернутого клинического анализа было установлено, что фенотип двоих детей, страдавших двусторонней косолапостью, характерен для больных с синдромом FTHS. Таким образом, исследование позволило безошибочно диагностировать синдром FTHS в семье, первоначально выбранной в связи с двусторонней косолапостью у ее членов, с помощью WES. Более того, наше исследование показало, что причиной развития синдрома FTHS с аутосомно-рецессивным типом наследования была вновь выявленная гомозиготная миссенсмутация (c.280C>G; p.R94G) в гене (NM_001308175.2) SH3PXD2B. Это служит дополнительным подтверждением существующих данных о том, что гомозиготные мутации в гене SH3PXD2B являются основной причиной развития синдрома FTHS.

Frank–Ter Haar syndrome (FTHS) is a rare genetic hereditary autosomal recessive disorder characterized by defective malformation of cardiovascular, craniofacial, and skeletal system. Mutations in the SH3PXD2B gene are a common cause in the development of FTHS. We recruited a family with two affected individuals (3-year-old female and 2-month-old male infant) having bilateral clubfoot. Family pedigree shows an autosomal recessive mode of inheritance. DNA was extracted from the blood samples of six members of the family. Whole exome sequencing was done for the two affected individuals and the variant was validated in the whole family by using Sanger sequencing approach. Whole exome sequencing (WES) data analysis identified a rare homozygous variant (c.280C>G; p.R94G) in the SH3PXD2B gene, and Sanger sequencing showed that the same variant perfectly segregates with the phenotype in the pedigree. Moreover, the variant is predicted to be damaging and deleterious by several computation tools. Revisiting the family members for detailed clinical analysis, we diagnosed the patients as having the typical phenotype of FTHS. This study enabled us to correctly diagnose the cases of FTHS in a family initially recruited for having bilateral clubfoot by using WES. Moreover, this study identified a novel homozygous missense variant (c.280C>G; p.R94G) in (NM_001308175.2) the SH3PXD2B gene as a causative variant for autosomal recessive FTHS. This finding supports the evidence that homozygous mutations in the SH3PXD2B gene are the main cause in the development of FTHS.

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