vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-68vavilov-4745Research ArticleМЕДИЦИНСКАЯ ЦИТОГЕНОМИКАMEDICAL CYTOGENOMICSРедкий случай однородительской дисомии хромосомы 9 в сочетании с мозаицизмомA rare case of uniparental disomy 9 concomitant with low-level mosaicismhttps://orcid.org/0009-0000-1110-732XЯковлеваА. С.IakovlevaA. S.

Москва

Moscow

shenkayter@icloud.comhttps://orcid.org/0000-0003-2941-2861МарковаЖ. Г.MarkovaZh. G.

Москва

Moscow

https://orcid.org/0000-0002-5946-4577БессоноваЛ. А.BessonovaL. A.

Москва

Moscow

https://orcid.org/0000-0002-0641-1084ШиловаН. В.ShilovaN. V.

Москва

Moscow

Медико-генетический научный центр им. академика Н.П. БочковаРоссияBochkov Research Centre for Medical GeneticsRussian Federation202504092025295629635Copyright © Яковлева А.С., Маркова Ж.Г., Бессонова Л.А., Шилова Н.В., 20252025Яковлева А.С., Маркова Ж.Г., Бессонова Л.А., Шилова Н.В.Iakovleva A.S., Markova Z.G., Bessonova L.A., Shilova N.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4745

   Однородительская дисомия хромосомы 9 в сочетании с мозаицизмом низкого уровня хромосомы 9 – редкое хромосомное нарушение. Один из механизмов формирования однородительской дисомии – коррекция анеуплоидии, приводящая также к мозаицизму низкого уровня. Трудности диагностики мозаичных анеуплоидий связаны с ограничениями в чувствительности и разрешающей способности стандартных цитогенетических методов, затрудняющих выявление мозаицизма низкого уровня. Различное соотношение клеточных линий в тканях пациента или неоднородность образцов одной и той же ткани не позволяют однозначно определить влияние мозаичной трисомии на формирование фенотипа пациента. Фенотипические признаки мозаичной трисомии 9 (Т9) отличаются широкой вариабельностью. В пренатальном периоде при этой хромосомной патологии часто отмечается внутриутробная задержка развития. У живорожденных с мозаицизмом по Т9 могут наблюдаться характерные фенотипические особенности, такие как черепно-лицевые аномалии (микрогнатия, аномалии ушей), сколиоз, низко посаженные уши, дисплазия тазобедренного сустава, судороги и задержка развития, а также проблемы с кормлением и дыханием. С целью установления диагноза у пациента с множественными стигмами дисэмбриогенеза и задержкой психомоторного развития проведено комплексное исследование молекулярно-цитогенетическими методами, включающее хромосомный микроматричный анализ (ХМА) высокого разрешения и флуоресцентную гибридизацию in situ (FISH) с таргетными ДНК-зондами. ХМА показал наличие участков потери гетерозиготности на хромосоме 9, свидетельствующее об однородительской дисомии, и позволил предположить мозаицизм низкого уровня по Т9. Дополнительный FISH-анализ культивированных лимфоцитов с ДНК-зондами на различные районы хромосомы 9 позволил установить мозаицизм низкого уровня по Т9. Результаты нашего исследования согласуются с представлением о том, что мозаицизм по хромосоме 9 в сочетании с однородительской дисомией является сложной генетической аномалией, которая может привести к задержке развития, нарушению роста и особенностям поведения. ХМА и FISH – это эффективные методы диагностики однородительской дисомии и мозаицизма низкого уровня по трисомии хромосомы 9.

   Uniparental disomy of chromosome 9, in combination with low-level mosaicism for chromosome 9, represents a rare chromosomal disorder. One of the mechanisms underlying the formation of uniparental disomy is the trisomy rescue, which concurrently results in low-level mosaicism. The diagnosis of mosaic aneuploidies poses significant challenges due to the limited sensitivity and resolution of conventional cytogenetic methods, which often fail to detect low-level mosaicism. Additionally, the variable distribution of cell lines within the patient’s tissues, as well as the heterogeneity of samples derived from the same tissue, complicates the precise determination of the impact of mosaic trisomy on the phenotypic expression. Phenotypic manifestations associated with mosaic trisomy 9 are characterized by considerable variability. During the prenatal period, intrauterine growth restriction is frequently observed in cases of this chromosomal abnormality, although this finding is not pathognomonic for the condition. In liveborn infants with trisomy 9 mosaicism, characteristic phenotypic features may include craniofacial anomalies (such as micrognathia and ear malformations), scoliosis, low-set ears, feeding and respiratory difficulties, hip dysplasia, seizures, and developmental delays. To establish a diagnosis in a patient presenting with multiple dysembryogenic stigmata and psychomotor retardation, a comprehensive molecular cytogenetic analysis was conducted. This included high-resolution chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) using targeted DNA probes. CMA identified regions of loss of heterozygosity (LOH) on chromosome 9, indicative of uniparental disomy, and suggested the presence of low-level mosaicism for trisomy 9. Subsequent FISH analysis of cultured lymphocytes, employing DNA probes specific to various regions of chromosome 9, confirmed the low-level mosaicism for trisomy 9. The results of our study are consistent with the idea that mosaicism for chromosome 9, particularly when combined with uniparental disomy, constitutes a complex genetic anomaly that can lead to a spectrum of phenotypic manifestations, including developmental delay, growth abnormalities, and behavioral anomalies. CMA and FISH are highly effective methods for the diagnosis of uniparental disomy and low-level mosaicism involving chromosome 9.

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