Delineating MT-ATP6-associated disease
| Autor: | Kei Murayama, Marni J. Falk, Joohyun Park, Felix Distelmaier, Holger Prokisch, Shi Yuqing, Matthis Synofzik, Stephanie Kleinle, Rebecca D. Ganetzky, Peter Freisinger, Elisa Floride, Boriana Büchner, Johannes A. Mayr, Tobias B. Haack, Ludger Schöls, Saskia B. Wortmann, Cornelia Kornblum, Thomas Klopstock, Georg M. Stettner, Claudia Stendel, Fang Fang, Angela Abicht, Christiane Neuhofer |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Ataxia Asymptomatic Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Retinitis pigmentosa medicine Genetics (clinical) 030304 developmental biology 0303 health sciences biology business.industry medicine.disease Heteroplasmy 3. Good health MT-ATP6 Cohort biology.protein Neurology (clinical) medicine.symptom Differential diagnosis business 030217 neurology & neurosurgery Retinopathy |
| Zdroj: | Neurology Genetics. 6:e393 |
| ISSN: | 2376-7839 |
| DOI: | 10.1212/nxg.0000000000000393 |
| Popis: | ObjectiveTo delineate the phenotypic and genotypic spectrum in carriers of mitochondrial MT-ATP6 mutations in a large international cohort.MethodsWe analyzed in detail the clinical, genetical, and neuroimaging data from 132 mutation carriers from national registries and local databases from Europe, USA, Japan, and China.ResultsWe identified 113 clinically affected and 19 asymptomatic individuals with a known pathogenic MT-ATP6 mutation. The most frequent mutations were m.8993 T > G (53/132, 40%), m.8993 T > C (30/132, 23%), m.9176 T > C (30/132, 23%), and m.9185 T > C (12/132, 9%). The degree of heteroplasmy was high both in affected (mean 95%, range 20%–100%) and unaffected individuals (mean 73%, range 20%–100%). Age at onset ranged from prenatal to the age of 75 years, but almost half of the patients (49/103, 48%) became symptomatic before their first birthday. In 28 deceased patients, the median age of death was 14 months. The most frequent symptoms were ataxia (81%), cognitive dysfunction (49%), neuropathy (48%), seizures (37%), and retinopathy (14%). A diagnosis of Leigh syndrome was made in 55% of patients, whereas the classic syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP) was rare (8%).ConclusionsIn this currently largest series of patients with mitochondrial MT-ATP6 mutations, the phenotypic spectrum ranged from asymptomatic to early onset multisystemic neurodegeneration. The degree of mutation heteroplasmy did not reliably predict disease severity. Leigh syndrome was found in more than half of the patients, whereas classic NARP syndrome was rare. Oligosymptomatic presentations were rather frequent in adult-onset patients, indicating the need to include MT-ATP6 mutations in the differential diagnosis of both ataxias and neuropathies. |
| Databáze: | OpenAIRE |
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