Journal article

Authors list: Nolte, Dagmar; Kang, Jun-Suk; Hofmann, Amrei; Schwaab, Eva; Kraemer, Heidrun H.; Mueller, Ulrich

Publication year: 2021

Pages: 4866-4873

Journal: Journal of Neurology

Volume number: 268

Issue number: 12

ISSN: 0340-5354

eISSN: 1432-1459

Open access status: Hybrid

DOI Link: https://doi.org/10.1007/s00415-021-10607-5

Publisher: Springer

Abstract: 
Adult-onset ataxias are a genetically and clinically heterogeneous group of movement disorders. In addition to nuclear gene mutations, sequence changes have also been described in the mitochondrial genome. Here, we present findings of mutation analysis of the mitochondrial gene MT-ATP6. We analyzed 94 patients with adult-onset spinocerebellar ataxia (SCA), including 34 sporadic cases. In all patients, common sequence changes found in SCAs such as repeat expansions and point mutations had been excluded previously. We found pathogenic MT-ATP variants in five of these patients (5.32%), two of whom were sporadic. Four of the five mutations have not previously been described in ataxias. All but one of these mutations affect transmembrane helices of subunit-alpha of ATP synthase. Two mutations (p.G16S, and p.P18S) disrupt transmembrane helix 1 (TMH1), one mutation (p.G167D) affects TMH5, and another one (p.L217P) TMH6. The fifth mutation (p.T96A) describes an amino acid change in close proximity to transmembrane helix 3 (TMH3). The level of heteroplasmy was either complete or very high ranging from 87 to 99%. The high prevalence of pathogenic MT-ATP6 variants suggests that analysis of this gene should be included in the routine workup of both hereditary and sporadic ataxias.

Harvard Citation style: Nolte, D., Kang, J., Hofmann, A., Schwaab, E., Kraemer, H. and Mueller, U. (2021) Mutations in MT-ATP6 are a frequent cause of adult-onset spinocerebellar ataxia, Journal of Neurology, 268(12), pp. 4866-4873. https://doi.org/10.1007/s00415-021-10607-5

APA Citation style: Nolte, D., Kang, J., Hofmann, A., Schwaab, E., Kraemer, H., & Mueller, U. (2021). Mutations in MT-ATP6 are a frequent cause of adult-onset spinocerebellar ataxia. Journal of Neurology. 268(12), 4866-4873. https://doi.org/10.1007/s00415-021-10607-5