Acta neurologica Scandinavica · 2020
Progressive external ophthalmoplegia associated with novel MT-TN mutations.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Visuttijai Kittichate, Hedberg-Oldfors Carola, Lindgren Ulrika, Nordström Sara, Elíasdóttir Ólöf, Lindberg Christopher, Oldfors Anders
Аннотация
OBJECTIVES: To describe two patients with progressive external ophthalmoplegia (PEO) and mitochondrial myopathy associated with mutations in mitochondrial DNA, encoding the tRNAAsn gene (MT-TN), which have not previously been published with clinical descriptions.
MATERIALS & METHODS: Two unrelated patients with PEO were clinically examined. Muscle biopsy was performed and investigated by exome sequencing, enzyme histochemistry, and immunohistochemistry. The level of heteroplasmy was investigated in single muscle fibers and in other tissues.
RESULTS: Patient 1 was a 52-year-old man with ptosis, PEO, and exercise intolerance since childhood. Muscle biopsy demonstrated mitochondrial myopathy with frequent cytochrome c oxidase (COX)-deficient fibers and a heteroplasmic mutation, m.5669G>A in the MT-TN gene, resulting in a substitution of a highly conserved C to T in the T stem of tRNAAsn . Patient 2 was a 66-year-old woman with ptosis, PEO, and exercise intolerance since many years. Muscle biopsy demonstrated mitochondrial myopathy with frequent COX-deficient fibers. She had a novel m.5702delA mutation in MT-TN, resulting in loss of a highly conserved U in the anticodon stem of tRNAAsn . Single fiber analysis in both cases showed highly significant differences in mutation load between COX-deficient and COX-normal fibers and a high threshold level for COX deficiency. The mutations were not found in blood, urine sediment or buccal cells.
CONCLUSION: We describe two MT-TN mutations associated with PEO and mitochondrial myopathy, and their pathogenicity was demonstrated. Together with previous reports, the results indicate that MT-TN is a hot spot for mutations causing sporadic PEO.
MATERIALS & METHODS: Two unrelated patients with PEO were clinically examined. Muscle biopsy was performed and investigated by exome sequencing, enzyme histochemistry, and immunohistochemistry. The level of heteroplasmy was investigated in single muscle fibers and in other tissues.
RESULTS: Patient 1 was a 52-year-old man with ptosis, PEO, and exercise intolerance since childhood. Muscle biopsy demonstrated mitochondrial myopathy with frequent cytochrome c oxidase (COX)-deficient fibers and a heteroplasmic mutation, m.5669G>A in the MT-TN gene, resulting in a substitution of a highly conserved C to T in the T stem of tRNAAsn . Patient 2 was a 66-year-old woman with ptosis, PEO, and exercise intolerance since many years. Muscle biopsy demonstrated mitochondrial myopathy with frequent COX-deficient fibers. She had a novel m.5702delA mutation in MT-TN, resulting in loss of a highly conserved U in the anticodon stem of tRNAAsn . Single fiber analysis in both cases showed highly significant differences in mutation load between COX-deficient and COX-normal fibers and a high threshold level for COX deficiency. The mutations were not found in blood, urine sediment or buccal cells.
CONCLUSION: We describe two MT-TN mutations associated with PEO and mitochondrial myopathy, and their pathogenicity was demonstrated. Together with previous reports, the results indicate that MT-TN is a hot spot for mutations causing sporadic PEO.