Clinical and genetic characteristics of ponto-cerebellar hypoplasia caused by mutations in the TSEN54 gene (OMIM: 277470)
E. I. Dadali,
I. A. Akimova,
N. A. Semenova,
D. M. Guseva,
O. A. Shchagina,
A. I. Chukhrova,
I. V. Kanivets,
S. A. Korostelev https://doi.org/10.17650/2222-8721-2019-9-2-30-36
Abstract
Introduction. The description of the clinical and genetic characteristics of eight patients with autosomal-recessive variant pontocerebellar hypoplasia due to mutations in the TSEN54 gene.
Purpose. Description of clinical and genetic characteristics of Russian patients with type 2A and type 4 of pontocerebellar hypoplasia.
Materials and methods. The diagnosis of pontocerebellar hypoplasia was established on the basis of the specific features of clinical manifestations and detection of mutations in the gene TSEN54 based on the analysis of the results of exome sequencing.
Results. 8 patients with pontocerebellar hypoplasia caused by mutations in the TSEN54 gene were identified.
Discussion. Based on the features of clinical manifestations and severity of the disease in 5 patients diagnosed pontocerebellar hypoplasia type 2A, and in 3 patients – type 4. In patients with type 2A of pontocerebellar hypoplasia discovered mutation c. 919G>T (p.Ala307Ser) in a homozygous state. Patients with type 4 of pontocerebellar hypoplasia this mutation is detected in the compound heterozygous state with c.670_671delAA (p.Lys224fs) and c.1264C>T (p.Gln422fs).
Conclusion. The obtained results allow us to conclude that, as well as in European populations, the mutation c.919G>T (p. Ala307Ser) is a major in Russian patients with pontocerebellar hypoplasia 2A and 4 types, which account for about half of all cases of this disease group. The search for this mutation should be the first stage of molecular genetic diagnosis in patients with clinical and magnetic resonance signs of pontocerebellar hypoplasia.
About the Authors
E. I. Dadali
Research Center of Medical Genetics
Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
1 Ostrovityanova St., Moscow, 117997, Russia
I. A. Akimova
Research Center of Medical Genetics
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
N. A. Semenova
Research Center of Medical Genetics
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
D. M. Guseva
Research Center of Medical Genetics
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
O. A. Shchagina
Research Center of Medical Genetics
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
A. I. Chukhrova
Research Center of Medical Genetics
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
Russian Federation
1 Moskvorech’e St., Moscow 115478, Russia
I. V. Kanivets
Genomed LLC
Russian medical Academy of continuous professional education, Ministry of Health of Russia
Russian Federation
Russian Federation
8A Podol’skoye Shosse, Moscow, 115093, Russia
Build. 1, 2 / 1 Barrikadnaya, Moscow, 125993. Russia
S. A. Korostelev
Genomed LLC
Russian Federation
8A Podol’skoye Shosse, Moscow, 115093, Russia
Russian Federation
8A Podol’skoye Shosse, Moscow, 115093, Russia
References
1. Namavar Y., Barth P.G., Kasher P.R. et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 2011;134(1):143–56. DOI: 10.1093/brain/awq287. PMID: 20952379.
2. Battini R., D’Arrigo S., Cassandrini D. et al. Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2. J Child Neurol 2014;29(4):520–5. DOI: 10.1177/0883073812470002. PMID: 23307886.
3. Bierhals T., Korenke G.C., Uyanik G., Kutsche K. Pontocerebellar hypoplasia type 2 TSEN2: rewiew of the literature and two novel mutations. Eur J Med Genet 2013;56:325–30. DOI: 10.1016/j.ejmg.2013.03.009. PMID: 23562994.
4. Cassandrini D., Biancheri R., Tessa A. et al. Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies. Neurology 2010;75:1459–64. DOI: 10.1212/WNL.0b013e3181f88173. PMID: 20956791.
5. Namavar Y., Barth P.G., Poll-The B.T., Baas F. Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia. Orphanet J Rare Dis 2011;6:50. DOI: 10.1186/1750-1172-6-50. PMID: 21749694.
6. Namavar Y., Chitayat D., Barth P.G. et al. TSEN54 mutations cause pontocerebellar hypoplasia type 5. Eur J Hum Genet 2011;19(6):724–6. DOI: 10.1038/ejhg.2011.8. PMID: 21368912.
7. Sánchez-Albisua I., Frölich S., Barth P.G. et al. Natural course of pontocerebellar hypoplasia type 2A. Orphanet J Rare Dis 2014;9(1):70. DOI: 10.1186/1750-1172-9-70. PMID: 24886362.
8. Brun R. Zur kenntnis der bildungsfehler des kleinhirns. Epikritische bemerkungen
9. zur entwicklungspathologie, morphologie und klinik der umschriebenen entwicklungshemmungen des neozerebellums. Schweiz. Arch Neurol Psychiatr 1917;1:48–105.
10. Koster S., Case I. Two cases of hypoplasia pontocerebellaris. Acta Psychiatr Scand 1926;1:47–83. DOI: 10.1111/j.1600-0447.1926.tb05648.x.
11. Van Dijk T., Baas F., Barth P.G et al. What’s new in pontocerebellar hypoplasia? An update on genes and subtypes. Orphanet Journal of Rare Diseases 2018;13:92. DOI: 10.1186/s13023-018-0826-2. PMID: 29903031.
12. Budde B.S., Namavar Y., Barth P.G. et al. tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nature Genet 2008;40:1113–8. DOI: 10.1038/ng.204.PMID: 18711368.
13. Paushkin S.V., Patel M., Furia B.S. et al. Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3-prime end formation. Cell 2004;117:311–21. DOI: 10.1016/S0092-8674(04)00342-3. PMID: 15109492.
14. Donis K.C., Mattos E.P., Silva A.A. et al. Infantile spinocerebellar ataxia type 7: case report and a review of the literature. J Neurol Sci 2015;354(1–2):118–21. DOI: 10.1016/j.jns.2015.04.04.
15. Singh A., Faruq M., Mukerji M. et al. Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases. J Child Neurol 2014;29(1):139–44. DOI: 10.1177/0883073813509015. PMID: 24300164.
16. Feraco P., Mirabelli-Badenier M., Severino M. et al. The shrunken, bright cerebellum: a characteristic MRI finding in congenital disorders of glycosylation type 1a. Am J Neuroradiol 2012;33(11): 2062–7. DOI: 10.3174/ajnr.A3151.
17. Boltshauser E., Doherty D. Cerebellar hypoplasia: differential diagnosis and diagnostic approach. Am J Med Genet Med Genet 2014;166(2):211–26. DOI: 10.1002/ajmg.c.31398. PMID: 24839100.
18. Fry A.E., Cushion T.D., Pilz D.T. The genetics of lissencephaly. Am J Med Genet Part C Semin Med Genet 2014;166(2):198–210. DOI: 10.1002/ajmg.c.31402. PMID: 24862549.
19. Hong S.E., Shugart Y.Y., Huang D.T. et al. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet 2000;26(1):93–6. DOI: 10.1038/79246. PMID: 10973257
Review
For citations:
Dadali E.I., Akimova I.A., Semenova N.A., Guseva D.M., Shchagina O.A., Chukhrova A.I., Kanivets I.V., Korostelev S.A. Clinical and genetic characteristics of ponto-cerebellar hypoplasia caused by mutations in the TSEN54 gene (OMIM: 277470). Neuromuscular Diseases. 2019;9(2):30-36. (In Russ.) https://doi.org/10.17650/2222-8721-2019-9-2-30-36
Views:
2046
Email this article 