Jansen J J, Maassen J A, van der Woude F J, Lemmink H A, van den Ouweland J M, t' Hart L M, Smeets H J, Bruijn J A, Lemkes H H
Department of Metabolic Diseases and Endocrinology, University Hospital Leiden, The Netherlands.
J Am Soc Nephrol. 1997 Jul;8(7):1118-24. doi: 10.1681/ASN.V871118.
Several studies show an association of a guanine for adenine substitution (A-->G) at position 3243 in mitochondrial DNA (mtDNA) with a recently recognized diabetic subtype designated maternally inherited diabetes and deafness (MIDD). This mutation shows heterogeneity in its phenotypic expression as is apparent from its association with several other syndromes. Screening for the 3243A-->G mutation in mtDNA was performed in those diabetic patients attending the Leiden University Hospital diabetics clinic who had a history of maternally inherited diabetes, sensorineural hearing loss, or both. Four individuals from three unrelated families were identified who suffered from progressive nondiabetic kidney disease in association with diabetes mellitus and hearing loss. The mode of inheritance suggested maternal transmission. The combination of renal failure and hearing loss had been misdiagnosed as Alport syndrome in three of the four individuals. Therefore, in addition to these three families, another 63 unrelated patients with possible Alport syndrome were selected at random. DNA from peripheral blood and other tissues from members of the three families and from the 63 additional Alport syndrome patients was examined for the presence of the 3243A-->G mutation in mtDNA. The mutation was detected in heteroplasmic form in the four patients and their maternal relatives. Also, one of the 63 suspected Alport syndrome patients showed heteroplasmy for the 3243 mutation. These data show the existence of a kidney disease that is characterized by the presence of the A-->G mutation at position 3243 in the mtDNA.
多项研究表明，线粒体DNA（mtDNA）第3243位的鸟嘌呤替代腺嘌呤（A→G）与一种最近才被认识的糖尿病亚型——母系遗传糖尿病伴耳聋（MIDD）相关。这种突变在表型表达上具有异质性，这从它与其他几种综合征的关联中就可以明显看出。对莱顿大学医院糖尿病门诊的糖尿病患者进行了mtDNA中3243A→G突变的筛查，这些患者有母系遗传糖尿病、感音神经性听力损失或两者兼有的病史。在三个无关家庭中发现了四名个体，他们患有与糖尿病和听力损失相关的进行性非糖尿病性肾病。遗传方式提示为母系遗传。在这四名个体中的三名中，肾衰竭和听力损失的组合被误诊为Alport综合征。因此，除了这三个家庭外，还随机选择了另外63名可能患有Alport综合征的无关患者。检测了来自这三个家庭的成员以及另外63名Alport综合征患者外周血和其他组织的DNA中mtDNA 3243A→G突变的存在情况。在四名患者及其母系亲属中检测到该突变呈异质性形式存在。此外，63名疑似Alport综合征患者中的一名也显示出3243突变的异质性。这些数据表明存在一种以mtDNA第3243位存在A→G突变为特征的肾脏疾病。
