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Клинический полиморфизм РАСопатий в условиях детского кардиологического отделения
Клинический полиморфизм РАСопатий в условиях детского кардиологического отделения
Мельник О.В., Гудкова А.Я., Вершинина Т.Л. и др. Клинический полиморфизм РАСопатий в условиях детского кардиологического отделения. Consilium Medicum. 2017; 19 (12): 100–104. DOI: 10.26442/2075-1753_19.12.100-104
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Аннотация
В статье представлены 7 клинических случаев РАСопатий, включая 2 летальных, манифестировавших гипертрофической кардиомиопатией разной степени тяжести (n=6) и некомпактным миокардом (n=1) в пре- и постнатальном периодах, наблюдавшихся в ФГБУ «НМИЦ им. В.А.Алмазова». У всех детей доминировала клиническая картина кардиомиопатии. Клинически синдром LEOPARD был диагностирован у 2 пациентов, лицевой дисморфизм имел место также в 2 случаях. При проведении таргетного секвенирования нового поколения на целевую панель 108 генов, ассоциированных с развитием врожденных заболеваний миокарда, кардиомиопатий и каналопатий, с последующим секвенированием по Сэнгеру, у пациентов обнаружены различные мутации в генах PTPN11, BRAF, CBL.
Ключевые слова: РАСопатии, гипертрофическая кардиомиопатия, некомпактный миокард, педиатрия, секвенирование нового поколения.
Key words: RASopathies, hypertrophic cardiomyopathy, noncompaction myocardium, pediatrics, next generation sequencing.
Ключевые слова: РАСопатии, гипертрофическая кардиомиопатия, некомпактный миокард, педиатрия, секвенирование нового поколения.
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Key words: RASopathies, hypertrophic cardiomyopathy, noncompaction myocardium, pediatrics, next generation sequencing.
Полный текст
Список литературы
1. Rauen K. The RASopathies. Ann Rev Genomics Hum Genetics 2013; 14: 355–69.
2. Aoki Y, Niihori T, Inoue S et al. Recent advances in RASopathies. J Hum Genetics 2016; 61: 33–9.
3. Yamamoto GL, Aguena M, Gos M et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genetics 2015; 52 (6): 413–21.
4. Aoki Y, Niihori T, Banjo T et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genetics 2013; 93 (1): 173–80.
5. Romano AA, Allanson JE, Dahlgren J et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126 (4): 746–59.
6. William ET, Rauen KA. Expansion of the RASopathies. Cur Genetic Med Reports 2016; 4 (3): 57–64.
7. Martinez-Quintana E, Rodriguez-Gonzalez F. LEOPARD syndrome: clinical features and gene mutations. Molecular Syndromology 2012; 3: 145–57.
8. Limongelli G, Pacileo G, Marino B et al. Prevalence and Clinical Significance of Cardiovascular Abnormalities in Patients With the LEOPARD Syndrome. Am J Cardiol 2007; 100: 736–41.
9. Allanson JE, Anneren G, Aoki Y et al. Cardio-facio-cutaneous syndrome: does genotype predict phenotype? Am J Med Genetics. Part C: Seminars in Medical Genetics 2011; 157: 129–35.
10. Lin AE, Alexander ME, Colan SD et al. Clinical, pathological, and molecular analysis of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. Am J Med Genetics. Part A 2011; 155: 486–507.
11. Sarkozy A, Didilio MC, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis 2008; 3 (1): 13.
12. Jorge AA, Malaquias AC, Arnhold IG et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Hormone Res 2009; 71: 185–93.
13. Wilkinson JD, Lowe AM, Salbert BA et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012; 164 (3): 442–8.
14. Sun X-L, Zhao J, Chen X et al. A Unique Case of a 12-Year-Old Boy with Noonan Syndrome Combined With Noncompaction of the Ventricular Myocardium. Int Heart J Assoc 2016; 57 (2): 258–61.
2. Aoki Y, Niihori T, Inoue S et al. Recent advances in RASopathies. J Hum Genetics 2016; 61: 33–9.
3. Yamamoto GL, Aguena M, Gos M et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genetics 2015; 52 (6): 413–21.
4. Aoki Y, Niihori T, Banjo T et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genetics 2013; 93 (1): 173–80.
5. Romano AA, Allanson JE, Dahlgren J et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126 (4): 746–59.
6. William ET, Rauen KA. Expansion of the RASopathies. Cur Genetic Med Reports 2016; 4 (3): 57–64.
7. Martinez-Quintana E, Rodriguez-Gonzalez F. LEOPARD syndrome: clinical features and gene mutations. Molecular Syndromology 2012; 3: 145–57.
8. Limongelli G, Pacileo G, Marino B et al. Prevalence and Clinical Significance of Cardiovascular Abnormalities in Patients With the LEOPARD Syndrome. Am J Cardiol 2007; 100: 736–41.
9. Allanson JE, Anneren G, Aoki Y et al. Cardio-facio-cutaneous syndrome: does genotype predict phenotype? Am J Med Genetics. Part C: Seminars in Medical Genetics 2011; 157: 129–35.
10. Lin AE, Alexander ME, Colan SD et al. Clinical, pathological, and molecular analysis of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. Am J Med Genetics. Part A 2011; 155: 486–507.
11. Sarkozy A, Didilio MC, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis 2008; 3 (1): 13.
12. Jorge AA, Malaquias AC, Arnhold IG et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Hormone Res 2009; 71: 185–93.
13. Wilkinson JD, Lowe AM, Salbert BA et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012; 164 (3): 442–8.
14. Sun X-L, Zhao J, Chen X et al. A Unique Case of a 12-Year-Old Boy with Noonan Syndrome Combined With Noncompaction of the Ventricular Myocardium. Int Heart J Assoc 2016; 57 (2): 258–61.
2. Aoki Y, Niihori T, Inoue S et al. Recent advances in RASopathies. J Hum Genetics 2016; 61: 33–9.
3. Yamamoto GL, Aguena M, Gos M et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genetics 2015; 52 (6): 413–21.
4. Aoki Y, Niihori T, Banjo T et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genetics 2013; 93 (1): 173–80.
5. Romano AA, Allanson JE, Dahlgren J et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126 (4): 746–59.
6. William ET, Rauen KA. Expansion of the RASopathies. Cur Genetic Med Reports 2016; 4 (3): 57–64.
7. Martinez-Quintana E, Rodriguez-Gonzalez F. LEOPARD syndrome: clinical features and gene mutations. Molecular Syndromology 2012; 3: 145–57.
8. Limongelli G, Pacileo G, Marino B et al. Prevalence and Clinical Significance of Cardiovascular Abnormalities in Patients With the LEOPARD Syndrome. Am J Cardiol 2007; 100: 736–41.
9. Allanson JE, Anneren G, Aoki Y et al. Cardio-facio-cutaneous syndrome: does genotype predict phenotype? Am J Med Genetics. Part C: Seminars in Medical Genetics 2011; 157: 129–35.
10. Lin AE, Alexander ME, Colan SD et al. Clinical, pathological, and molecular analysis of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. Am J Med Genetics. Part A 2011; 155: 486–507.
11. Sarkozy A, Didilio MC, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis 2008; 3 (1): 13.
12. Jorge AA, Malaquias AC, Arnhold IG et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Hormone Res 2009; 71: 185–93.
13. Wilkinson JD, Lowe AM, Salbert BA et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012; 164 (3): 442–8.
14. Sun X-L, Zhao J, Chen X et al. A Unique Case of a 12-Year-Old Boy with Noonan Syndrome Combined With Noncompaction of the Ventricular Myocardium. Int Heart J Assoc 2016; 57 (2): 258–61.
________________________________________________
2. Aoki Y, Niihori T, Inoue S et al. Recent advances in RASopathies. J Hum Genetics 2016; 61: 33–9.
3. Yamamoto GL, Aguena M, Gos M et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genetics 2015; 52 (6): 413–21.
4. Aoki Y, Niihori T, Banjo T et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genetics 2013; 93 (1): 173–80.
5. Romano AA, Allanson JE, Dahlgren J et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126 (4): 746–59.
6. William ET, Rauen KA. Expansion of the RASopathies. Cur Genetic Med Reports 2016; 4 (3): 57–64.
7. Martinez-Quintana E, Rodriguez-Gonzalez F. LEOPARD syndrome: clinical features and gene mutations. Molecular Syndromology 2012; 3: 145–57.
8. Limongelli G, Pacileo G, Marino B et al. Prevalence and Clinical Significance of Cardiovascular Abnormalities in Patients With the LEOPARD Syndrome. Am J Cardiol 2007; 100: 736–41.
9. Allanson JE, Anneren G, Aoki Y et al. Cardio-facio-cutaneous syndrome: does genotype predict phenotype? Am J Med Genetics. Part C: Seminars in Medical Genetics 2011; 157: 129–35.
10. Lin AE, Alexander ME, Colan SD et al. Clinical, pathological, and molecular analysis of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. Am J Med Genetics. Part A 2011; 155: 486–507.
11. Sarkozy A, Didilio MC, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis 2008; 3 (1): 13.
12. Jorge AA, Malaquias AC, Arnhold IG et al. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Hormone Res 2009; 71: 185–93.
13. Wilkinson JD, Lowe AM, Salbert BA et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012; 164 (3): 442–8.
14. Sun X-L, Zhao J, Chen X et al. A Unique Case of a 12-Year-Old Boy with Noonan Syndrome Combined With Noncompaction of the Ventricular Myocardium. Int Heart J Assoc 2016; 57 (2): 258–61.
Авторы
О.В.Мельник*1, А.Я.Гудкова1,2, Т.Л.Вершинина1, И.Л.Никитина1, А.А.Костарева1, Т.М.Первунина1
1 ФГБУ «Национальный медицинский исследовательский центр им. В.А.Алмазова» Минздрава России. 197341, Россия, Санкт-Петербург, ул. Аккуратова, д. 2;
2 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России. 197022, Россия, Санкт-Петербург, ул. Льва Толстого, д. 6/8
*orangelove@yandex.ru
1 V.A.Almazov National Medical Research Centre. 197341, Russian Federation, Saint Petersburg, ul. Akkuratova, d. 2;
2 I.P.Pavlov First Saint Petersburg State Medical University of the Ministry of Health of the Russian Federation. 197022, Russian Federation, Saint Petersburg, ul. L'va Tolstogo, d. 6/8
*orangelove@yandex.ru
1 ФГБУ «Национальный медицинский исследовательский центр им. В.А.Алмазова» Минздрава России. 197341, Россия, Санкт-Петербург, ул. Аккуратова, д. 2;
2 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России. 197022, Россия, Санкт-Петербург, ул. Льва Толстого, д. 6/8
*orangelove@yandex.ru
________________________________________________
1 V.A.Almazov National Medical Research Centre. 197341, Russian Federation, Saint Petersburg, ul. Akkuratova, d. 2;
2 I.P.Pavlov First Saint Petersburg State Medical University of the Ministry of Health of the Russian Federation. 197022, Russian Federation, Saint Petersburg, ul. L'va Tolstogo, d. 6/8
*orangelove@yandex.ru
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