vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2020-65-3-328-341vestib-692Research ArticleСтатьиРоль генетических нарушений в формировании инвалидизирующих последствий у недоношенного новорожденногоThe role of genetic disorders in the formation of disabling effects in the premature newbornМалышеваО. М.MalyshavaV. M.

Малышева Ольга Михайловна - аспирант, младший научный сотрудник.

ул. Академическая, 27, 220072, Минск.

Volha M. Malyshava - Postgraduate student, Junior Researcher, Institute of Genetics and Cytology of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.

O.Malysheva@igc.byМихаленкоЕ. П.MikhalenkaA. P.

Михаленко Елена Петровна - кандидат биологических наук, ведущий научный сотрудник.

ул. Академическая, 27, 220072, Минск.

Alena P. Mikhalenka - Ph. D. (Biol.), Leading Researcher, Institute of Genetics and Cytology of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.

E.Michalenko@igc.byСухареваА. П.SuharavaA. P.

Сухарева Анастасия Павловна - аспирант, врач-неонатолог.

ул. Ф. Скорины, 16, 220114, Минск.

Anastasiya P. Suharava - Postgraduate student, Neo-natologist, Clinical Maternity Hospital of Minsk Region.

16, F. Skorinu Str., 220114, Minsk.

nstbor@tut.byАртюшевскаяМ. В.ArtsiusheuskayaM. V.

Артюшевская Марина Владимировна - кандидат медицинских наук, ассистент.

ул. П. Бровки, 3/3, 220013, Минск.

Maryna V. Artsiusheuskaya - Ph. D. (Med.), Assistant, Belarusian Medical Academy of Postgraduate Education.

3/3, P Brovkа Str., 220013, Minsk.

6579542@bk.ruСитникН. Г.SitnikN. G.

Ситник Надежда Геннадьевна - аспирант, врач-реаниматолог.

ул. Ф. Скорины, 16, 220114, Минск.

Nadzeya G. Sitnik - Postgraduate student, Resuscitator, Clinical Maternity Hospital of Minsk Region.

16, F. Skorina Str., 220114, Minsk.

n.g.sitnik@gmail.comКулаковаГ. В.KulakovaG V.

Кулакова Галина Валерьевна - врач анестезиолог-реаниматолог.

ул. Ф. Скорины, 16, 220114, Минск.

Galina V. Kulakova - Resuscitation anesthetist, Clinical Maternity Hospital of Minsk Region.

16, F. Skorinа Str., 220114, Minsk.

dockulakova@gmail.comЖевнеронокИ. В.GhevneronakI. V.

Жевнеронок Ирина Владимировна - кандидат медицинских наук, доцент.

ул. П. Бровки, 3/3, 220013, Минск.

Iryna V. Ghevneronak - Ph. D. (Med.), Assistant Professor, Belarusian Medical Academy of Postgraduate Education.

3/3, P. Brovka Str., 220013, Minsk.

ira_jevner@tut.byКильчевскийА. В.KilchevskyA. V.

Кильчевский Александр Владимирович - академик, доктор биологических наук, профессор.

ул. Академическая, 27, 220072, Минск.

Aleksandr V. Kilchevsky - Academician, D. Sc. (Biol.), Professor, Institute of Genetics and Cytology of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.

Kilchev@presidium.bas-net.byШишкоГ. А.ShyshkoG. A.

Шишко Георгий Александрович - доктор медицинских наук, профессор.

ул. П. Бровки, 3/3, 220013, Минск.

Georgiy A. Shyshko - D. Sc. (Med.), Professor, Belarusian Medical Academy of Postgraduate Education.

3/3, P. Brovkа Str., 220013, Minsk.

georg_shishko@mail.ruИнститут генетики и цитологии НАН БеларусиInstitute of Genetics and Cytology of the National Academy of Sciences of BelarusКлинический родильный дом Минской областиClinical Maternity Hospital of Minsk RegionБелорусская медицинская академия последипломного образованияBelarusian Medical Academy of Postgraduate Education202006082020653328341Copyright © Малышева О.М., Михаленко Е.П., Сухарева А.П., Артюшевская М.В., Ситник Н.Г., Кулакова Г.В., Жевнеронок И.В., Кильчевский А.В., Шишко Г.А., 20202020Малышева О.М., Михаленко Е.П., Сухарева А.П., Артюшевская М.В., Ситник Н.Г., Кулакова Г.В., Жевнеронок И.В., Кильчевский А.В., Шишко Г.А.Malyshava V.M., Mikhalenka A.P., Suharava A.P., Artsiusheuskaya M.V., Sitnik N.G., Kulakova G.V., Ghevneronak I.V., Kilchevsky A.V., Shyshko G.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/692

Представлен клинический случай проявления первичной врожденной глаукомы, синдрома дыхательных расстройств, бронхолегочной дисплазии, ретинопатии и перивентрикулярной лейкомаляции у недоношенного новорожденного. Для поиска патогенных вариантов использован метод высокопроизводительного полноэкзом-ного секвенирования. Учитывая данные о многофакторной этиологии исследуемых осложнений, проанализированы гены белков сурфактанта и гены, ассоциированные с ангиогенезом, ренин-ангиотензиновой и антиоксидантной системами. Выявлены молекулярно-генетические факторы риска развития врожденной глаукомы у недоношенного новорожденного: p.E229K CYP1B1 и p.R76K MYOC, а также полиморфные варианты в генах белков сурфактанта SFTPB (rs1130866, VNTR интрона 4) и SFTPC (rs4715, rs1124), фактора роста эндотелия сосудов VEGFA (rs2010963), синтазы оксида азота 3 NOS3 (rs1799983), белка связывания инсулиноподобного фактора роста 3 IGFBP3 (rs2854746), каталазы CAT (rs7943316), ассоциированных с развитием исследуемых инвалидизирующих осложнений.

A clinical case of primary congenital glaucoma, respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy and periventricular leukomalacia in a premature newborn is presented. The search for pathogenic variants by the method of new generation whole exome sequencing was performed. The genes of surfactant proteins, genes associated with angiogenesis, renin-angiotensin and antioxidant systems were analyzed, considering the data on the multifactorial etiology of the studied complications. The molecular genetic factors for congenital glaucoma development in the premature newborn were revealed: p.E229K CYP1B1 and p.R76K MYOC, as well as polymorphisms in the genes of surfactant proteins SFTPB (rs1130866, VNTR intron 4) and SFTPC (rs4715, rs1124), vascular endothelial growth factor VEGFA (rs2010963), nitric oxide synthase 3 NOS3 (rs1799983), insulin growth factor binding protein 3 IGFBP3 (rs2854746), catalase CAT (rs7943316), associated with the development of the studied disabling complications in the premature newborn.

 

недоношенные новорожденныесиндром дыхательных расстройствбронхолегочная дисплазияретинопатияглаукомасеквенированиеprematurityrespiratory distress syndromebronchopulmonary dysplasiaretinopathy of prematurityglaucomasequencingReferencesIdentifying risk factors shared by bronchopulmonary dysplasia, severe retinopathy, and cystic periventricular leukomalacia in very preterm infants for targeted intervention / L.-W. Wang [et al.] // Neonatology. - 2018. - Vol. 114. -P. 17-24. https://doi.org/10.1159/000487505Wang L.-W., Lin Y.-C., Wang S.-T., Huang C.-C. Identifying risk factors shared by bronchopulmonary dysplasia, severe retinopathy, and cystic periventricular leukomalacia in very preterm infants for targeted intervention. Neonatology, 2018, vol. 114, no. 1, pp. 17-24. https://doi.org/10.1159/000487505CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States / S.-H. Lim [et al.] // Am. J. Ophthalmol. - 2013. - Vol. 155, N 3. - P. 508-517.e5. https://doi.org/10.1016/j.ajo.2012.09.012Lim S.-H., Tran-Viet K. N., Yanovitch T. L., Freedman S. F., Klemm T., Call W., Powell C., Ravichandran A., Metlapally R., Nading E. B., Rozen S., Young T. L. CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States. American Journal of Ophthalmology, 2013, vol. 155, no. 3, pp. 508-517.e5. https://doi.org/10.1016/j.ajo.2012.09.012Giuffre, I. Molecular analysis of Italian patients with congenital glaucoma / I. Giuffre // Glaucoma - current clinical and research aspects / ed. P. Gunvant. - Rijeka, 2011. - P. 71-82.Giuffre I. Molecular analysis of Italian patients with congenital glaucoma. Glaucoma - current clinical and research aspects. Rijeka, 2011, pp. 71-82.Sambrook, J. Isolation of high-molecular-weight DNA from mammalian cells / J. Sambrook, E. F. Fritsch, T. Maniatis // Molecular cloning: a laboratory manual. - 2nd ed. - New York, 1989. - P. 9.14-9.23.Sambrook J., Fritsch E. F., Maniatis T. Isolation of high-molecular-weight DNA from mammalian cells. Molecular Cloning: a laboratory manual. 2nd ed. New York, 1989, pp. 9.14-9.23.Chang, X. wANNOVAR: annotating genetic variants for personal genomes via the web / X. Chang, K. Wang // J. Med. Gen. - 2012. - Vol. 49, N 7. - P. 433-436. https://doi.org/10.1136/jmedgenet-2012-100918Chang X., Wang K. wANNOVAR: annotating genetic variants for personal genomes via the web. Journal of Medical Genetics, 2012, vol. 49, no. 7, pp. 433-436. https://doi.org/10.1136/jmedgenet-2012-100918Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of primary open-angle glaucoma / J. Chen [et al.] // Mol. Vis. - 2011. - Vol. 17. - P. 1431-1435.Chen J., Cai S. P., Yu W., Yan N., Tang L., Chen X., Liu X. Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of primary open-angle glaucoma. Molecular Vision, 2011, vol. 17, pp. 1431-1435.World medical association declaration of Helsinki: ethical principles for medical research involving human subjects / World Med. Assoc. // JAMA. - 2013. - Vol. 310, N 20. - P. 2191-2194. https://doi.org/10.1001/jama.2013.281053World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA, 2013, vol. 310, no. 20, pp. 2191-2194. https://doi.org/10.1001/jama.2013.281053Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss / E. Souzeau [et al.] // JAMA Ophthalmol. - 2015. - Vol. 133, N 7. - P. 826-833. https://doi.org/10.1001/jamaophthalmol.2015.0980Souzeau E., Hayes M., Zhou T., Siggs O. M., Ridge B., Awadalla M. S. [et al.]. Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss. JAMA Ophthalmology, 2015, vol. 133, no. 7, pp. 826-833. https://doi.org/10.1001/jamaophthalmol.2015.0980Shah, B. R. Cytochrome P450 1B1: role in health and disease and effect of nutrition on its expression / B. R. Shah, W. Xu, J. Mraz // RSC Adv. - 2019. - Vol. 9, N 36. - P. 21050-21062. https://doi.org/10.1039/C9RA03674AShah B. R., Xu W., Mraz J. Cytochrome P450 1B1: role in health and disease and effect of nutrition on its expression. RSC Advances, 2019, vol. 9, no. 36, pp. 21050-21062. https://doi.org/10.1039/C9RA03674AIdentification of four novel cytochrome P4501B1 mutations (p.I94X, p.H279D, p.Q340H, and p.K433K) in primary congenital glaucoma patients / M. Tanwar [et al.] // Mol. Vis. - 2009. - Vol. 15. - P. 2926-2937.Tanwar M., Dada T., Sihota R., Dada R. Identification of four novel cytochrome P4501B1 mutations (p.I94X, p.H279D, p.Q340H, and p.K433K) in primary congenital glaucoma patients. Molecular Vision, 2009, vol. 15, pp. 2926-2937.Molecular basis for involvement of CYP1B1 in MYOC upregulation and its potential implication in glaucoma pathogenesis / S. Mookherjee [et al.] // PLoS ONE. - 2012. - Vol. 7. - Art. e45077. https://doi.org/10.1371/journal.pone.0045077Mookherjee S., Acharya M., Banerjee D., Bhattacharjee A., Ray K. Molecular basis for involvement of CYP1B1 in MYOC upregulation and its potential implication in glaucoma pathogenesis. PLoS ONE, 2012, vol. 7, no. 9, art. e45077. https://doi.org/10.1371/journal.pone.0045077Role of CYP1B1 p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma / V. Gupta [et al.] // Graefe's Arch. Clin. Exp. Ophthalmol. - 2017. - Vol. 256, N 2. - P. 355-362. https://doi.org/10.1007/s00417-017-3853-0Gupta V., Somarajan B. I., Walia G. K., Kaur J., Kumar S., Gupta S. [et al.]. Role of CYP1B1 p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma. Graefe's Archive for Clinical and Experimental Ophthalmology, 2017, vol. 256, no. 2, pp. 355-362. https://doi.org/10.1007/s00417-017-3853-0Somarajan BI2, Walia GK3, Kaur J4, Kumar S4, Gupta S2, Chaurasia AK2, Gupta D5, Kaushik A5, Mehta A2, Gupta V6, Sharma A7. CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians / J. Beuten [et al.] // Carcinogenesis. - 2008. - Vol. 29. - P. 1751-1757. https://doi.org/10.1093/carcin/bgm300Beuten J., Gelfond J. A., Byrne J. J., Balic I., Crandall A. C., Johnson-Pais T. L., Thompson I. M., Price D. K., Leach R. J. CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians. Carcinogenesis, 2008, vol. 29, no. 9, pp. 1751-1757. https://doi.org/10.1093/carcin/bgm300Астахов, Ю. С. Наследственность и глаукома / Ю. С. Астахов, В. В. Рахманов // Офтальмол. ведомости. - 2012. -Т. 5, № 4. - C. 51-57.Astakhov Yu. S., Rakhmanov V. V. Heredity and glaucoma. Oftal'mologicheskie vedomosti [Ophthalmology journal], 2012, vol. 5, no. 4, pp. 51-57 (in Russian).Старикова, Д. И. Генетические исследования при первичной открытоугольной глаукоме / Д. И. Старикова, М. И. Чурносов // РМЖ. Клин. офтальмология. - 2017. - Т. 17, № 1. - С. 49-52.Starikova D. I., Churnosov M. I. Genetic studies in primary open-angle glaucoma. RMZh. Klinicheskaya oftal'mologiya = Russian Journal of Clinical Ophthalmology, 2017, vol. 17, no. 1, pp. 49-52 (in Russian).Population-based frequency of surfactant dysfunction mutations in a native Chinese cohort Population / Y.-J. Chen [et al.] // World J. Pediatr. - 2015. - Vol. 12, N 2. - P. 190-195. https://doi.org/10.1007/s12519-015-0047-xChen Y.-J., Wambach J. A., Pass K., Wegner D. J., Chen S.-K., Zhang Q.-Y., Heins H., Cole F. S., Hamvas A. Populationbased frequency of surfactant dysfunction mutations in a native Chinese cohort population. World Journal of Pediatrics, 2015, vol. 12, no. 2, pp. 190-195. https://doi.org/10.1007/s12519-015-0047-xAssociation of a vascular endothelial growth factor polymorphism with the development of bronchopulmonary dysplasia in Japanese premature newborns / K. Fujioka [et al.] // Sci. Reports. - 2015. - Vol. 4. - Art. 4459. https://doi.org/10.1038/srep04459Fujioka K., Shibata A., Yokota T., Koda T., Nagasaka M., Yagi M., Takeshima Y., Yamada H., Iijima K., Morioka I. Association of a vascular endothelial growth factor polymorphism with the development of bronchopulmonary dysplasia in Japanese premature newborns. Scientific Reports, 2015, vol. 4, art. 4459. https://doi.org/10.1038/srep04459Genetic contributions to the development of complications in preterm newborns / C. Poggi [et al.] // PLoS ONE. -2015. - Vol. 10, N 7. - Art. e0131741. https://doi.org/10.1371/journal.pone.0131741Poggi C., Giusti B., Gozzini E., Sereni A., Romagnuolo I., Kura A., Pasquini E., Abbate R., Dani C. Genetic contributions to the development of complications in preterm newborns. PLoS ONE, 2015, vol. 10, no. 7, art. e0131741. https://doi.org/10.1371/journal.pone.0131741The genetics of retinopathy of prematurity: a model for neovascular retinal disease / R. Swan [et al.] // Ophthalmol. Retina. - 2018. - Vol. 2, N 9. - P. 949-962. https://doi.org/10.1016/j.oret.2018.01.016Swan R., Kim S. J., Campbell J. P., Chan R. V. P., Sonmez K., Taylor K. D. [et al.]. The genetics of retinopathy of prematurity: a model for neovascular retinal disease. Ophthalmology Retina, 2018, vol. 2, no. 9, pp. 949-962. https://doi.org/10.1016/j.oret.2018.01.016Association of IGF-1 CA(n) and IGFBP3 rs2854746 polymorphisms with endometrial polyp risk / P. Leopoldo [et al.] // BioMed Res. Int. - 2018. - Vol. 2018. - Art. 8704346. https://doi.org/10.1155/2018/8704346Leopoldo P., Doria S., Moscovitz T., Tcherniakovsky M., Fernandes C. E., Pompei L. M., Wajman M., Nimwegen A., Haimovich S. Association of IGF-1 CA(n) and IGFBP3 rs2854746 polymorphisms with endometrial polyp risk. BioMed Research International, 2018, vol. 2018, art. 8704346. https://doi.org/10.1155/2018/8704346A pathogenic relationship of bronchopulmonary dysplasia and retinopathy of prematurity? A review of angiogenic mediators in both diseases / A. Stark [et al.] // Front. Pediatr. - 2018. - Vol. 6. - Art. 125. https://doi.org/10.3389/fped.2018.00125Stark A., Dammann C., Nielsen H. C., Volpe M. V. A pathogenic relationship of bronchopulmonary dysplasia and retinopathy of prematurity? A review of angiogenic mediators in both diseases. Frontiers in Pediatrics, 2018, vol. 6, art. 125. https://doi.org/10.3389/fped.2018.00125Endothelial nitric oxide synthase gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome / M. A.-W. Albeshery [et al.] // Int. J. Res. Med. Sci. - 2016. - Vol. 4, N 12. - P. 5382-5386. https://doi.org/10.18203/2320-6012.ijrms20164214Albeshery M. A.-W., Abdel-Haie O. M., Ramadan N. S., Mohammed S. A. Endothelial nitric oxide synthase gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome. International Journal of Research in Medical Sciences, 2016, vol. 4, no. 12, pp. 5382-5386. https://doi.org/10.18203/2320-6012.ijrms20164214Superoxide dismutase 3, extracellular (SOD3) variants and lung function / K. Ganguly [et al.] // Physiol. Genom. -2009. - Vol. 37, N 3. - P. 260-267. https://doi.org/10.1152/physiolgenomics.90363.2008Ganguly K., Depner M., Fattman C., Bein K., Oury T. D., Wesselkamper S. C. [et al.]. Superoxide dismutase 3, extracellular (SOD3) variants and lung function. Physiological Genomics, 2009, vol. 37, no. 3, pp. 260-267. https://doi.org/10.1152/physiolgenomics.90363.2008Association of rs1800668 polymorphism in glutathione peroxidase-1 gene and risk of rheumatoid arthritis in Pakistani population / S. Irfan [et al.] // Pak. J. Med. Sci. - 2016. - Vol. 32, N 5. - P. 1204-1207. http://dx.doi.org/10.12669/pjms.325.10325Irfan S., Rani A., Sameem M., Nawaz S. K., Liaqat I., Arshad M. Association of rs1800668 polymorphism in glutathione peroxidase-1 gene and risk of rheumatoid arthritis in Pakistani population. Pakistan Journal of Medical Sciences, 2016, vol. 32, no. 5, pp. 1204-1207. http://dx.doi.org/10.12669/pjms.325.10325Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants / B. Giusti [et al.] // Free Radic. Res. - 2012. - Vol. 46, N 9. - P. 1130-1139. https://doi.org/10.3109/10715762.2012.692787Giusti B., Vestrini A., Poggi C., Magi A., Pasquini E., Abbate R., Dani C. Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants. Free Radical Research, 2012, vol. 46, no. 9, pp. 1130-1139. https://doi.org/10.3109/10715762.2012.692787Association of catalase polymorphisms with primary open-angle glaucoma in a Chinese population / B. Gong [et al.] // Ophthalmic Genetics. - 2017. - Vol. 39, N 1. - P. 35-40. http://dx.doi.org/10.1080/13816810.2017.1342132Gong B., Shi Y., Qu C., Ye Z., Yin Y., Tan C., Shuai P., Li J., Guo X., Cheng Y., Yang Z., Lin Y., Liu X. Association of catalase polymorphisms with primary open-angle glaucoma in a Chinese population. Ophthalmic Genetics, 2017, vol. 39, no. 1, pp. 35-40. http://dx.doi.org/10.1080/13816810.2017.1342132Роль VEGF в развитии неопластического ангиогенеза / В. П. Чехонин [и др.] // Вестн. Рос. акад. мед. наук. -2012. - Т. 67, № 2. - C. 23-34.Chekhonin V. P., Shein S. A., Korchagina A. A., Gurina O. I. The role of VEGF in the development of neoplastic angiogenesis. Vestnik Rossiiskoi akademii meditsinskikh nauk = Annals of the Russian academy of medical sciences, 2012, vol. 67, no. 2, pp. 23-34 (in Russian).ACE gene deletion/deletion polymorphism may be a protective factor for respiratory distress in preterm infants / E. Sivasli [et al.] // Turk. J. Pediatr. - 2007. - Vol. 49, N 1. - P. 69-74.SivasliE., Yurdakok M., Babaoglu E., Karabulut H., Yigit S., Babaoglu M., Tekinalp G., Tukun A. ACE gene deletion/ deletion polymorphism may be a protective factor for respiratory distress in preterm infants. Turkish Journal of Pediatrics, 2007, vol. 49, no. 1, pp. 69-74.

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