Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority

Chamova, Teodora; Todorov, Tihomir; Palaima, Paulius; Yankova, Petya; Pacheva, Iliyana; Ivanov, Ivan; Georgieva, Bilyana; Cherninkova, Sylvia; Savov, Alexey; Zlatareva, Dora; Naumova, Elisaveta; Todorova, Albena; Jordanova, Albena; Tournev, Ivailo

doi:10.3390/genes16060641

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Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority

by

Teodora Chamova

^1,*

,

Tihomir Todorov

²,

Paulius Palaima

^3,4,†,

Petya Yankova

⁵,

Iliyana Pacheva

^6,7,8

,

Ivan Ivanov

^6,7,8

,

Bilyana Georgieva

⁹,

Sylvia Cherninkova

¹,

Alexey Savov

¹⁰,

Dora Zlatareva

¹¹,

Elisaveta Naumova

⁴,

Albena Todorova

^2,9,

Albena Jordanova

^3,4,9

and

Ivailo Tournev

^1,12

¹

Department of Neurology, University Hospital “Alexandrovska”, Medical University, 1431 Sofia, Bulgaria

²

Genetic Medico-Diagnostic Laboratory “Genica”, 1431 Sofia, Bulgaria

³

Molecular Neurogenomics Group, VIB Center for Molecular Neurology, VIB, 2610 Antwerp, Belgium

⁴

Molecular Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium

⁵

Department of Clinical Immunology, University Hospital “Alexandrovska”, Medical University, 1431 Sofia, Bulgaria

⁶

Department of Pediatrics, University Hospital “St George”, 4000 Plovdiv, Bulgaria

⁷

Department of Pediatrics, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria

⁸

Research Institute at Medical University of Plovdiv, 4000 Plovdiv, Bulgaria

⁹

Department of Medical Chemistry and Biochemistry, Medical University, 1431 Sofia, Bulgaria

¹⁰

National Genetic Laboratory, Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University, 1431 Sofia, Bulgaria

¹¹

Department of Diagnostic imaging, University Hospital “Alexandrovska”, Medical University, 1431 Sofia, Bulgaria

¹²

Department of Cognitive Science and Psychology, New Bulgarian University, 1618 Sofia, Bulgaria

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^*

Author to whom correspondence should be addressed.

^†

Current address: Thermo Fisher Scientific, Vyduno g 2, 06204 Vilnius, Lithuania.

Genes 2025, 16(6), 641; https://doi.org/10.3390/genes16060641

Submission received: 4 May 2025 / Revised: 16 May 2025 / Accepted: 22 May 2025 / Published: 27 May 2025

(This article belongs to the Special Issue Advances in Neurogenetics and Neurogenomics)

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Abstract

Background: Ataxia–telangiectasia (A-T) is a rare autosomal recessive disorder due to mutations in the ATM gene. Given the residual kinase activity and the type of ATM mutation, its clinical spectrum varies from a severe classic phenotype to a variant atypical form. Material and methods: This study included 28 patients belonging to four big Bulgarian Muslim pedigrees with tremor and dystonia. Whole-exome sequencing was performed in seven affected individuals from two unrelated pedigrees, followed by Sanger sequencing of the coding sequences and exon–intron borders of the ATM gene. Results: Twenty-four of the affected individuals were homozygous for c.8147T>C (p.Val2716Ala) in ATM, while four of the affected individuals were compound heterozygous. The targeted Sanger sequencing along the ATM gene revealed as a second mutation in three of the patients the splice-site variant c.4909+1G>A and in one patient a synonymous pathogenic variant with a splicing effect, c.3576G>A, p.Lys1192. The age at onset in our group varied between 14 days and 40 years. The main symptoms were dystonia and tremor, more prominent in the upper limbs and the neck, and dystonic dysarthria and dysphagia. The clinical course was very slowly progressive. Brain imaging was normal in the majority of the patients. Conclusion: Clinical features due to mutations in the ATM gene can be very broad. The disease may appear as dystonia, especially of early onset, without frank cerebellar involvement and also normal cerebral imaging. A-T should be considered in all patients with unexplained, even mild movement disorders and elevated α fetoprotein.

Keywords: tremor–dystonia; АТМ gene; Bulgarian Muslims; WES

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MDPI and ACS Style

Chamova, T.; Todorov, T.; Palaima, P.; Yankova, P.; Pacheva, I.; Ivanov, I.; Georgieva, B.; Cherninkova, S.; Savov, A.; Zlatareva, D.; et al. Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority. Genes 2025, 16, 641. https://doi.org/10.3390/genes16060641

AMA Style

Chamova T, Todorov T, Palaima P, Yankova P, Pacheva I, Ivanov I, Georgieva B, Cherninkova S, Savov A, Zlatareva D, et al. Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority. Genes. 2025; 16(6):641. https://doi.org/10.3390/genes16060641

Chicago/Turabian Style

Chamova, Teodora, Tihomir Todorov, Paulius Palaima, Petya Yankova, Iliyana Pacheva, Ivan Ivanov, Bilyana Georgieva, Sylvia Cherninkova, Alexey Savov, Dora Zlatareva, and et al. 2025. "Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority" Genes 16, no. 6: 641. https://doi.org/10.3390/genes16060641

APA Style

Chamova, T., Todorov, T., Palaima, P., Yankova, P., Pacheva, I., Ivanov, I., Georgieva, B., Cherninkova, S., Savov, A., Zlatareva, D., Naumova, E., Todorova, A., Jordanova, A., & Tournev, I. (2025). Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority. Genes, 16(6), 641. https://doi.org/10.3390/genes16060641

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Variant Ataxia–Telangiectasia Presenting as Tremor–Dystonia Syndrome in a Bulgarian Religious Minority

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