Chinnery Patrick F, DiMauro Salvatore, Shanske Sara, Schon Eric A, Zeviani Massimo, Mariotti Caterina, Carrara Fanco, Lombes Anne, Laforet Pascal, Ogier Helène, Jaksch Michaela, Lochmüller Hanns, Horvath Rita, Deschauer Marcus, Thorburn David R, Bindoff Laurence A, Poulton Joanna, Taylor Robert W, Matthews John N S, Turnbull Douglass M
Neurology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Lancet. 2004;364(9434):592-6. doi: 10.1016/S0140-6736(04)16851-7.
Pathogenic mitochondrial DNA (mtDNA) mutations are found in at least one in 8000 individuals. No effective treatment for mtDNA disorders is available, making disease prevention important. Many patients with mtDNA disease harbour a single pathogenic mtDNA deletion, but the risk factors for new cases and disease recurrence are not known.
We did a multicentre study of 226 families in which a single mtDNA deletion had been identified in the proband, including patients with chronic progressive external ophthalmoplegia, Kearns Sayre syndrome, or Pearson's syndrome. We studied the relation between maternal age and the risk of unaffected mothers having an affected child, and determined the recurrence risks among the siblings and offspring of affected individuals.
We noted no relation between maternal age and the risk of unaffected mothers having children with an mtDNA deletion disorder. None of the 251 siblings of the index cases developed clinical features of mtDNA disease. Risk of recurrence among the offspring of affected women was 4.11% (95% CI 0.86-11.54, or one in 117 to one in nine births). Only one of the mothers who had an affected child had a duplication of mtDNA in skeletal muscle.
Unlike nuclear chromosomal rearrangements, incidence of mtDNA deletion disorders does not increase with maternal age, and unaffected mothers are unlikely to have more than one affected child. Affected women were previously thought to have a negligible chance of having clinically affected offspring, but the actual risk is, on average, about one in 24 births.
致病性线粒体DNA（mtDNA）突变在每8000人中至少有1人存在。目前尚无针对mtDNA疾病的有效治疗方法，因此疾病预防至关重要。许多患有mtDNA疾病的患者存在单个致病性mtDNA缺失，但新发病例和疾病复发的危险因素尚不清楚。
我们对226个家庭进行了一项多中心研究，这些家庭的先证者中已鉴定出单个mtDNA缺失，包括慢性进行性外眼肌麻痹、卡恩斯·塞尔综合征或皮尔逊综合征患者。我们研究了母亲年龄与未受影响母亲生育患病子女风险之间的关系，并确定了受影响个体的兄弟姐妹和后代中的复发风险。
我们发现母亲年龄与未受影响母亲生育患有mtDNA缺失疾病子女的风险之间没有关系。索引病例的251名兄弟姐妹均未出现mtDNA疾病的临床特征。受影响女性后代的复发风险为4.11%（95%置信区间0.86 - 11.54，即每117次生育中有1次至每9次生育中有1次）。只有一名生育了患病子女的母亲在骨骼肌中存在mtDNA重复。
与核染色体重排不同，mtDNA缺失疾病的发病率不会随母亲年龄增加，未受影响的母亲不太可能生育超过一个患病子女。此前认为受影响女性生育临床受影响后代的几率可忽略不计，但实际风险平均约为每24次生育中有1次。
