Neuro-Ophthalmology Division (ARC, NRM), Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; GeneDx (HC, KA, AB, RB), Gaithersburg, Maryland; and Department of Genetic Medicine (HJV), Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Neuroophthalmol. 2024 Jun 1;44(2):247-252. doi: 10.1097/WNO.0000000000001984. Epub 2023 Sep 4.
Establishing a molecular diagnosis of mitochondrial diseases due to pathogenic mitochondrial DNA (mtDNA) variants can be difficult because of varying levels of tissue heteroplasmy, and identifying these variants is important for clinical management. Here, we present clinical and molecular findings in 8 adult patients with classical features of mitochondrial ophthalmologic and/or muscle disease and multiple mtDNA deletions isolated to muscle.
The patients were identified via a retrospective review of patients seen in both a tertiary ophthalmology center and a genetics clinic with a clinical diagnosis of chronic progressive external ophthalmoplegia, optic nerve abnormalities, and/or mitochondrial myopathy. Age at onset of symptoms ranged from 18 to 61 years. Ocular manifestations included bilateral optic neuropathy in one patient, bilateral optic disc cupping without optic neuropathy in 2 patients, ptosis in 4 patients, and ocular motility deficits in 2 patients. Five patients had generalized weakness.
Pathogenic variants in mtDNA were not found in the blood or buccal sample from any patient, but 7 of 8 patients had multiple mtDNA deletions identified in muscle tissue. One patient had a single mtDNA deletion identified in the muscle. Heteroplasmy was less than 15% for all of the identified deletions, with the exception of one deletion that had a heteroplasmy of 50%-60%. None of the patients were found to have a nuclear gene variant known to be associated with mitochondrial DNA maintenance.
mtDNA deletions were identified in adult patients with ophthalmologic and/or musle abnormalities and may underlie their clinical presentations.
由于组织异质性的程度不同，建立致病性线粒体 DNA（mtDNA）变异引起的线粒体疾病的分子诊断可能具有挑战性，并且鉴定这些变异对于临床管理很重要。在这里，我们介绍了 8 例具有经典线粒体眼病和/或肌肉病特征且肌肉中存在多种 mtDNA 缺失的成年患者的临床和分子发现。
通过回顾性分析在一家三级眼科中心和一家遗传学诊所就诊的具有慢性进行性外眼肌麻痹、视神经异常和/或线粒体肌病临床诊断的患者，确定了这些患者。症状的发病年龄从 18 岁到 61 岁不等。眼部表现包括 1 例双侧视神经病变，2 例双侧视盘凹陷而无视神经病变，4 例上睑下垂，2 例眼球运动障碍。5 例患者有全身无力。
在任何患者的血液或口腔样本中均未发现 mtDNA 中的致病性变异，但 8 例患者中有 7 例在肌肉组织中发现了多种 mtDNA 缺失。1 例患者的肌肉中发现了单个 mtDNA 缺失。所有鉴定出的缺失中异质性均小于 15%，除了一个缺失的异质性为 50%-60%。未发现任何与 mtDNA 维持相关的核基因突变。
在具有眼科和/或肌肉异常的成年患者中鉴定出 mtDNA 缺失，这些缺失可能是其临床表现的基础。
