Research Unit of Clinical Neuroscience University of Oulu Oulu Finland.
Medical Research Center Oulu Oulu University Hospital and University of Oulu Oulu Finland.
Brain Behav. 2017 Nov 19;7(12):e00859. doi: 10.1002/brb3.859. eCollection 2017 Dec.
Mutations in mitochondrial DNA cause a variety of clinical phenotypes ranging from a mild hearing impairment (HI) to severe encephalomyopathy. The gene is a hotspot for mutations causing HI. The m.7510T>C mutation in has been previously associated with non-syndromic HI in four families from different ethnic backgrounds.
We describe the clinical, genetic, and histopathological findings in a Finnish family with the heteroplasmic m.7510T>C mutation in mitochondrial DNA.
The family proband presented with a progressive mitochondrial disease phenotype including migraine, epilepsy, mild ataxia, and cognitive impairment in addition to HI. One young adult presented with HI only. Other family members had a mild phenotype comprising ataxia and tremor in addition to HI. Mutation heteroplasmy was 90% in the blood of maternal grandmother and ≥99% in the muscle and blood of the three other family members. Muscle histology was consistent with mitochondrial myopathy in three family members. The mitochondrial haplogroup of the family was a different branch of the haplogroup H than in the previous reports of this mutation.
Our results suggest that, in addition to sensorineural HI, the m.7510T>C mutation is associated with a spectrum of mitochondrial disease clinical features including migraine, epilepsy, cognitive impairment, ataxia, and tremor, and with evidence of mitochondrial myopathy.
线粒体 DNA 突变可引起多种临床表型，从轻度听力障碍（HI）到严重的脑肌病。 基因是导致 HI 的突变热点。先前已有研究报道，在来自不同种族背景的四个家族中，线粒体 DNA 中的 m.7510T>C 突变与非综合征性 HI 相关。
我们描述了一个芬兰家族的临床、遗传和组织病理学发现，该家族存在线粒体 DNA 异质性 m.7510T>C 突变。
该家系先证者表现为进行性线粒体疾病表型，除 HI 外，还伴有偏头痛、癫痫、轻度共济失调和认知障碍。一名年轻成人仅表现为 HI。其他家族成员的表型较轻，除 HI 外，还伴有共济失调和震颤。母系外祖母的血液中突变异质性为 90%，其他三位家族成员的肌肉和血液中异质性为≥99%。三名家族成员的肌肉组织学符合线粒体肌病。该家族的线粒体单倍群是与先前报道的该突变不同的 H 单倍群的一个分支。
我们的结果表明，除了感觉神经性 HI 之外，m.7510T>C 突变还与一系列线粒体疾病的临床特征相关，包括偏头痛、癫痫、认知障碍、共济失调和震颤，并伴有线粒体肌病的证据。
