Нервно-мышечные болезни. 2024; 14: 42-50
Особенности клинических проявлений и генетических характеристик синдрома Шаафа–Янга у российских пациентов
https://doi.org/10.17650/2222-8721-2024-14-1-42-50Аннотация
Представлено описание клинико‑генетических характеристик 4 российских пациентов с синдромом Шаафа–Янга, обусловленным ранее описанными и вновь выявленными нуклеотидными вариантами в гене MAGEL2. Показано, что наиболее тяжелые клинические проявления обнаружены у пациента с вновь выявленным вариантом с.1828С>T (p.Gln610Ter), в то время как у пациента с новым нуклеотидным вариантом с.1609С>T (p.Gln537Ter) проявления болезни выражены умеренно. С учетом значительного сходства клинических проявлений синдрома Шаафа–Янга с таковыми синдрома Прадера–Вилли изложены критерии их дифференциальной диагностики, использование которых поможет оптимизировать процесс молекулярно‑генетического анализа, направленного на поиск этиологического фактора.
Список литературы
1. Schaaf C.P., Gonzalez-Garay M.L., Xia F. et al. Truncating mutations of MAGEL2 cause Prader–Willi phenotypes and autism. Nat Genet 2013;45 (11):1405–8. DOI: 10.1038/ng.2776
2. Fountain M.D., Aten E., Cho M.T. et al. The phenotypic spectrum of Schaaf–Yang syndrome: 18 new affected individuals from 14 families. Genet Med 2017;19(1):45–52. DOI: 10.1038/gim.2016.53
3. Fountain M.D., Schaaf C.P. Prader–Willi syndrome and Schaaf– Yang syndrome: Neurodevelopmental diseases intersecting at the MAGEL2 gene. Diseases 2016;4(1):2. DOI: 10.3390/diseases4010002
4. McCarthy J., Lupo P.J., Kovar E. et al. Schaaf–Yang syndrome overview: Report of 78 individuals. Am J Med Genet A 2018;176(12): 2564–74. DOI: 10.1002/ajmg.a.40650
5. Godler D.E., Butler M.G. Special issue: Genetics of Prader–Willi syndrome. Genes (Basel) 2021;12(9):1429. DOI: 10.3390/genes12091429
6. Patak J., Gilfert J., Byler M. et al. MAGEL2-related disorders: A study and case series. Clin Genet 2019;96(6):493–505. DOI: 10.1111/cge.13620
7. Tacer K.F., Potts P.R. Cellular and disease functions of the Prader– Willi syndrome gene MAGEL2. Biochem J 2017;474:2177–90. DOI: 10.1042/BCJ20160616
8. Lee S., Kozlov S., Hernandez L. et al. Expression and imprinting of MAGEL2 suggest a role in Prader–Willi syndrome and the homologous murine imprinting phenotype. Hum Mol Genet 2000;9(12): 1813–9. DOI: 10.1093/hmg/9.12.1813
9. Crutcher E., Pal R., Naini F. et al. mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf–Yang syndrome. Sci Rep 2019;9:15935. DOI: 10.1038/s41598-019-52287-2
10. Abreu A.P., Dauber A., Macedo D.B. et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. New Eng J Med 2013;368:2467–75. DOI: 10.1056/NEJMoa1302160
11. Schaaf C.P., Marbach F.. Schaaf–Yang syndrome. 2021 In: GeneReviews®. Seattle: University of Washington, 1993–2023.
12. McCarthy J., Lupo P.J., Kovar E. et al. Schaaf–Yang syndrome overview: Report of 78 individuals. Am J Med Genet 2018;176A:2564–74. DOI: 10.1002/ajmg.a.40650
13. Negishi Y., Ieda D., Hori I. et al. Schaaf–Yang syndrome shows a Prader–Willi syndrome-like phenotype during infancy. Orphanet J Rare Dis 2019;14:277. DOI: 10.1186/s13023-019-1249-4
14. Mejlachowicz D., Nolent F., Maluenda J.et al. Truncating mutations of MAGEL2, a gene within the Prader–Willi locus, are responsible for severe arthrogryposis. Am J Human Gen 2015;97(4):616–20. DOI: 10.1016/j.ajhg.2015.08.010
15. Marbach F., Elgizouli M., Rech M. et al. The adult phenotype of Schaaf–Yang syndrome. Orphanet J Rare Dis 2020;15:294. DOI: 10.1186/s13023-020-01557-8
16. Guo W., Nie Y., Yan Z. et al. Genetic testing and PGD for unexplained recurrent fetal malformations with MAGEL2 gene mutation. Sci China Life Sci 2019;62:886–94. DOI: 10.1007/s11427-019-9541-0
17. Kanber D., Giltay J., Wieczorek D. et al. A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader–Willi syndrome. Eur J Hum Genet 2009;17(5):582–90. DOI: 10.1038/ejhg.2008.232
18. Butler M.G. Prader–Willi syndrome and chromosome 15q11.2 BP1–BP2 region: A review. Int J Mol Sci 2023;24(5):4271. DOI: 10.3390/ijms24054271
19. Buiting K., Di Donato N., Beygo J. et al. Clinical phenotypes of MAGEL2 mutations and deletions. Orphanet J Rare Diss 2014;9:40. DOI: 10.1186/1750-1172-9-40
Neuromuscular Diseases. 2024; 14: 42-50
Special clinical manifestations and genetic characteristics of schaaf–Yang syndrome in Russian patients
https://doi.org/10.17650/2222-8721-2024-14-1-42-50Abstract
A description of the clinical and genetic characteristics of four Russian patients with Schaaf–Yang syndrome, caused by previously described and newly identified nucleotide variants in MAGEL2 gene, is presented. It was shown that the most severe clinical manifestations were found in a patient with the new identified variant c.1828C>T (p.Gln610Ter), while in a patient with a new nucleotide variant c.1609C>T (p.Gln537Ter) the manifestations of the disease were moderate. Considering the significant similarity of the clinical manifestations of Schaaf–Yang syndrome with Prader–Willi syndrome, the criteria for their differential diagnosis are outlined, the use of which will help optimize the process of molecular genetic analysis aimed at finding the etiologic factor.
References
1. Schaaf C.P., Gonzalez-Garay M.L., Xia F. et al. Truncating mutations of MAGEL2 cause Prader–Willi phenotypes and autism. Nat Genet 2013;45 (11):1405–8. DOI: 10.1038/ng.2776
2. Fountain M.D., Aten E., Cho M.T. et al. The phenotypic spectrum of Schaaf–Yang syndrome: 18 new affected individuals from 14 families. Genet Med 2017;19(1):45–52. DOI: 10.1038/gim.2016.53
3. Fountain M.D., Schaaf C.P. Prader–Willi syndrome and Schaaf– Yang syndrome: Neurodevelopmental diseases intersecting at the MAGEL2 gene. Diseases 2016;4(1):2. DOI: 10.3390/diseases4010002
4. McCarthy J., Lupo P.J., Kovar E. et al. Schaaf–Yang syndrome overview: Report of 78 individuals. Am J Med Genet A 2018;176(12): 2564–74. DOI: 10.1002/ajmg.a.40650
5. Godler D.E., Butler M.G. Special issue: Genetics of Prader–Willi syndrome. Genes (Basel) 2021;12(9):1429. DOI: 10.3390/genes12091429
6. Patak J., Gilfert J., Byler M. et al. MAGEL2-related disorders: A study and case series. Clin Genet 2019;96(6):493–505. DOI: 10.1111/cge.13620
7. Tacer K.F., Potts P.R. Cellular and disease functions of the Prader– Willi syndrome gene MAGEL2. Biochem J 2017;474:2177–90. DOI: 10.1042/BCJ20160616
8. Lee S., Kozlov S., Hernandez L. et al. Expression and imprinting of MAGEL2 suggest a role in Prader–Willi syndrome and the homologous murine imprinting phenotype. Hum Mol Genet 2000;9(12): 1813–9. DOI: 10.1093/hmg/9.12.1813
9. Crutcher E., Pal R., Naini F. et al. mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf–Yang syndrome. Sci Rep 2019;9:15935. DOI: 10.1038/s41598-019-52287-2
10. Abreu A.P., Dauber A., Macedo D.B. et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. New Eng J Med 2013;368:2467–75. DOI: 10.1056/NEJMoa1302160
11. Schaaf C.P., Marbach F.. Schaaf–Yang syndrome. 2021 In: GeneReviews®. Seattle: University of Washington, 1993–2023.
12. McCarthy J., Lupo P.J., Kovar E. et al. Schaaf–Yang syndrome overview: Report of 78 individuals. Am J Med Genet 2018;176A:2564–74. DOI: 10.1002/ajmg.a.40650
13. Negishi Y., Ieda D., Hori I. et al. Schaaf–Yang syndrome shows a Prader–Willi syndrome-like phenotype during infancy. Orphanet J Rare Dis 2019;14:277. DOI: 10.1186/s13023-019-1249-4
14. Mejlachowicz D., Nolent F., Maluenda J.et al. Truncating mutations of MAGEL2, a gene within the Prader–Willi locus, are responsible for severe arthrogryposis. Am J Human Gen 2015;97(4):616–20. DOI: 10.1016/j.ajhg.2015.08.010
15. Marbach F., Elgizouli M., Rech M. et al. The adult phenotype of Schaaf–Yang syndrome. Orphanet J Rare Dis 2020;15:294. DOI: 10.1186/s13023-020-01557-8
16. Guo W., Nie Y., Yan Z. et al. Genetic testing and PGD for unexplained recurrent fetal malformations with MAGEL2 gene mutation. Sci China Life Sci 2019;62:886–94. DOI: 10.1007/s11427-019-9541-0
17. Kanber D., Giltay J., Wieczorek D. et al. A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader–Willi syndrome. Eur J Hum Genet 2009;17(5):582–90. DOI: 10.1038/ejhg.2008.232
18. Butler M.G. Prader–Willi syndrome and chromosome 15q11.2 BP1–BP2 region: A review. Int J Mol Sci 2023;24(5):4271. DOI: 10.3390/ijms24054271
19. Buiting K., Di Donato N., Beygo J. et al. Clinical phenotypes of MAGEL2 mutations and deletions. Orphanet J Rare Diss 2014;9:40. DOI: 10.1186/1750-1172-9-40
