Over the last decade there have been major advances in our understanding of the genetic basis of mitochondrial disease, enabling genetic counseling for patients with autosomal dominant and autosomal recessive disorders. Genetic counseling for patients with mitochondrial DNA (mtDNA) mutations is less well established. Approximately one-third of adults with a mtDNA disorder are sporadic cases, usually due to a single deletion of mtDNA. About two-thirds of adults with mtDNA disease harbor a maternally transmitted point mutation. The recurrence risks are well documented for homoplasmic mtDNA mutations causing Leber hereditary optic neuropathy, but the situation is less clear for families with heteroplasmic mtDNA disorders. Two large studies have shown that for some heteroplasmic point mutations there appears to be a relationship between the percentage level of mutant mtDNA in a mother's blood and her risk of having clinically affected offspring. The situation is less clear for other point mutations, some of which may cause sporadic disease. Recent evidence has cast light on the general principles behind the transmission of heteroplasmic mtDNA point mutations, which may be important for genetic counseling in the future.

中文翻译：

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线粒体疾病的遗传

在过去十年中，我们对线粒体疾病遗传基础的理解取得了重大进展，为常染色体显性遗传和常染色体隐性遗传疾病患者提供了遗传咨询。对线粒体 DNA (mtDNA) 突变患者的遗传咨询尚不完善。大约三分之一患有 mtDNA 疾病的成年人是散发病例，通常是由于 mtDNA 的单个缺失。大约三分之二患有 mtDNA 疾病的成年人携带母系传播的点突变。导致 Leber 遗传性视神经病变的同质 mtDNA 突变的复发风险有据可查，但对于患有异质 mtDNA 疾病的家庭，情况不太清楚。两项大型研究表明，对于某些异质性点突变，母亲血液中突变 mtDNA 的百分比水平与其后代临床受影响的风险之间似乎存在关系。其他点突变的情况不太清楚，其中一些可能导致散发性疾病。最近的证据揭示了异质性 mtDNA 点突变传播背后的一般原则，这可能对未来的遗传咨询很重要。