Molecular epidemiology of hereditary ataxia in Finland
| Autor: | Harri Rusanen, Laura Kytövuori, Ari Siitonen, Joose Raivo, Joonas Lipponen, Kari Majamaa, Markku Laakso, Maria Lehtilahti, Hiroshi Doi, Mervi Ryytty, Fumiaki Tanaka, Seppo Helisalmi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Mitochondrial DNA
congenital hereditary and neonatal diseases and abnormalities Ataxia Cerebellar Ataxia CANVAS medicine Humans Replication Protein C RC346-429 Exome Finland Spinocerebellar Degenerations Genetics Molecular epidemiology Cerebellar ataxia business.industry Research Point mutation General Medicine Repeat expansion medicine.disease Hereditary ataxia Neurology (clinical) Neurology. Diseases of the nervous system medicine.symptom Trinucleotide repeat expansion business Polyneuropathy |
| Zdroj: | BMC Neurology, Vol 21, Iss 1, Pp 1-6 (2021) BMC Neurology |
| Popis: | Background The genetics of cerebellar ataxia is complex. Hundreds of causative genes have been identified, but only a few cause more than single cases. The spectrum of ataxia-causing genes differs considerably between populations. The aim of the study was to investigate the molecular epidemiology of ataxia in the Finnish population. Patients and methods All patients in hospital database were reviewed for the diagnosis of unspecified ataxia. Acquired ataxias and nongenetic ataxias such as those related to infection, trauma or stroke were excluded. Sixty patients with sporadic ataxia with unknown etiology and 36 patients with familial ataxia of unknown etiology were recruited in the study. Repeat expansions in the SCA genes (ATXN1, 2, 3, 7, 8/OS, CACNA1A, TBP), FXN, and RFC1 were determined. Point mutations in POLG, SPG7 and in mitochondrial DNA (mtDNA) were investigated. In addition, DNA from 8 patients was exome sequenced. Results A genetic cause of ataxia was found in 33 patients (34.4%). Seven patients had a dominantly inherited repeat expansion in ATXN8/OS. Ten patients had mitochondrial ataxia resulting from mutations in nuclear mitochondrial genes POLG or RARS2, or from a point mutation m.8561C > G or a single deletion in mtDNA. Interestingly, five patients were biallelic for the recently identified pathogenic repeat expansion in RFC1. All the five patients presented with the phenotype of cerebellar ataxia, neuropathy, and vestibular areflexia (CANVAS). Moreover, screening of 54 patients with Charcot-Marie-Tooth neuropathy revealed four additional patients with biallelic repeat expansion in RFC1, but none of them had cerebellar symptoms. Conclusions Expansion in ATXN8/OS results in the majority of dominant ataxias in Finland, while mutations in RFC1 and POLG are the most common cause of recessive ataxias. Our results suggest that analysis of RFC1 should be included in the routine diagnostics of idiopathic ataxia and Charcot-Marie-Tooth polyneuropathy. |
| Databáze: | OpenAIRE |
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