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
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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
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