vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-70vavilov-4748Research ArticleМЕДИЦИНСКАЯ ЦИТОГЕНОМИКАMEDICAL CYTOGENOMICSСемейный случай интерстициальной делеции короткого плеча хромосомы 6p22.3-p24.3 у близнецов с грубой задержкой психо-речевого развитияA familial case of interstitial deletion of the short arm of chromosome 6p22.3-p24.3 in twins with severe delay in psychomotor and speech developmenthttps://orcid.org/0000-0003-0924-5082МосквитинГ. Д.MoskvitinG. D.

Якутск

Yakutsk

Moskvitin.gavriil@mail.ruhttps://orcid.org/0000-0001-9698-0258КочкинаД. Б.KochkinaD. B.

Якутск

Yakutsk

ГуриноваЕ. Е.GurinovaE. E.

Якутск

Yakutsk

https://orcid.org/0000-0002-0295-3230ФедотовД. А.FedotovD. A.

Томск

Tomsk

https://orcid.org/0000-0001-5310-1217БекеневаЛ. В.BekenievaL. V.

Якутск

Yakutsk

https://orcid.org/0000-0002-0716-4302КашевароваА. А.KashevarovaA. A.

Томск

Tomsk

https://orcid.org/0000-0002-2079-0148СухомясоваА. Л.SukhomyasovaA. L.

Якутск

Yakutsk

https://orcid.org/0000-0002-0482-8046ЛебедевИ. Н.LebedevI. N.

Томск

Tomsk

https://orcid.org/0000-0002-8258-7452МаксимоваН. Р.MaximovaN. R.

Якутск

Yakutsk

Северо-восточный федеральный университет им. М.К. Аммосова; Государственное автономное учреждение Республики Саха (Якутия) «Республиканская больница № 1 – Национальный центр медицины им. М.Е. Николаева»РоссияM.K. Ammosov North-Eastern Federal University; M.E. Nikolaev Republic Hospital No. 1 – National Center of MedicineRussian FederationСеверо-восточный федеральный университет им. М.К. АммосоваРоссияM.K. Ammosov North-Eastern Federal UniversityRussian FederationНаучно-исследовательский институт медицинской генетики Томского национального исследовательского медицинского центра Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation202504092025295644651Copyright © Москвитин Г.Д., Кочкина Д.Б., Гуринова Е.Е., Федотов Д.А., Бекенева Л.В., Кашеварова А.А., Сухомясова А.Л., Лебедев И.Н., Максимова Н.Р., 20252025Москвитин Г.Д., Кочкина Д.Б., Гуринова Е.Е., Федотов Д.А., Бекенева Л.В., Кашеварова А.А., Сухомясова А.Л., Лебедев И.Н., Максимова Н.Р.Moskvitin G.D., Kochkina D.B., Gurinova E.E., Fedotov D.A., Bekenieva L.V., Kashevarova A.A., Sukhomyasova A.L., Lebedev I.N., Maximova N.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4748

   Интерстициальные делеции короткого плеча хромосомы 6 встречаются еще реже, чем дистальные делеции 6p24-pter с частотой 1:1 000 000 (по данным MalaCards, https://www.malacards.org/), и ассоциируются с задержками развития, расстройствами аутистического спектра, врожденными аномалиями, а также дисморфическими особенностями.

   Цель нашего исследования заключалась в поиске хромосомной патологии у близнецов из якутской семьи с грубой задержкой психоречевого развития, умственной отсталостью в сочетании с дисморфиями и врожденными аномалиями.

   В этой работе мы сообщаем о двух новых пациентах – монозиготных близнецах из одной якутской семьи, которым была проведена микроматричная сравнительная геномная гибридизация (aCGH). В результате диагностики обнаружена редкая интерстициальная делеция в регионе 6p22.3-p24.3 размером 7.5 Мб, которая ретроспективно была подтверждена анализом GTG – дифференциального окрашивания хромосом. По данным цитогенетического исследования, кариотипы родителей были нормальными, что говорит о de novo структурной хромосомной перестройке у пациентов. Также мы выполнили сравнительный фенотипический анализ этих близнецов между собой и с другими ранее описанными в литературе пациентами, у которых были найдены перекрывающиеся делеции в регионе 6р22-р24. Кроме того, проведены обзор литературы и анализ генного состава делетированного региона 6p22.3-p24.3 с обсуждением корреляции генотип-фенотип. По результатам фенотипического анализа выявлены как общие, так и различные стигмы дизморфогенеза, такие как краниофациальные дисморфии, деформации ушных раковин и отклонения в развитии верхних и нижних конечностей, часто упоминаемые в литературе. Однако в проанализированных данных как в литературе, так и в наших наблюдениях у всех пациентов отсутствовал общий делетированный регион в области 6p22-p24, что создает трудности в установлении точного диагноза. Полученные результаты указывают на сложность однозначного определения минимально перекрывающегося региона, ответственного за наблюдаемые фенотипические и поведенческие особенности, и на важность последовательного и многоуровневого подхода к диагностике грубой задержки психо-речевого развития.

   Interstitial deletions of the short arm of chromosome 6 are even rarer than distal deletions of 6p24-pter, with an incidence rate of 1:1,000,000 (according to MalaCards, https://www.malacards.org/). These deletions are associated with developmental delays, autism spectrum disorders, congenital anomalies, and dysmorphic features.

   The objective of our study was to identify chromosomal abnormalities in twins from a Yakut family exhibiting severe psycho-speech developmental delays, intellectual disability combined with dysmorphisms, and congenital anomalies.

   In this paper, two new cases involving monozygotic twins from a Yakut family, who underwent array comparative genomic hybridization (aCGH), were reported. The diagnostic results revealed a rare interstitial deletion in the region 6p22.3-p24.3, measuring 7.5 Mb, which was subsequently confirmed using a conventional cytogenetics (GTG-banding) method. According to the cytogenetic analysis, the karyotypes of the parents were normal, indicating a de novo structural chromosomal rearrangement in the patients. Additionally, a comparative phenotypic analysis of these twins with each other and with other previously reported patients was performed; they were found to have overlapping deletions in the 6p22-p24 region. Furthermore, a literature review and an analysis of the gene content of the deleted region 6p22.3-p24.3 were conducted, and so was a discussion of the genotype-phenotype correlation. The results of the phenotypic analysis revealed both common and distinct dysmorphogenic features, including craniofacial dysmorphisms, deformities of the auricles, and abnormalities in the development of the upper and lower limbs, which are often mentioned in the literature. However, the analyzed data, both from the literature and our observations, showed that all patients lacked a common deleted region in the 6p22-p24 area, creating challenges in establishing an accurate diagnosis. The findings indicate the complexity of defining the minimally overlapping region responsible for the observed phenotypic and behavioral traits and highlight the importance of a systematic and multi-level approach to diagnosing severe psycho-speech developmental delays.

интерстициальная делеция 6p22.3-p24.3интеллектуальные расстройствазадержка психо-речевого развитиярасстройство аутистического спектрамикроматричная сравнительная геномная гибридизацияinterstitial deletion 6p22.3-p24.3intellectual disorderspsychomotor and speech delayautism spectrum disordermicroarray comparative genomic hybridizationАнализ хромосомных микрочипов был проведен при поддержке гранта РНФ № 21-65-00017, https://rscf.ru/en/project/21-65-00017/ Клинико-генеалогические и цитогенетические исследования пациентов были проведены за счет государственного бюджета. 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The authors declare that there are no conflicts of interest present.