Hirano M, Garcia-de-Yebenes J, Jones A C, Nishino I, DiMauro S, Carlo J R, Bender A N, Hahn A F, Salberg L M, Weeks D E, Nygaard T G
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Am J Hum Genet. 1998 Aug;63(2):526-33. doi: 10.1086/301979.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare, multisystem disorder characterized clinically by ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility, leukoencephalopathy, thin body habitus, and myopathy. Laboratory studies reveal defects of oxidative-phosphorylation and multiple mtDNA deletions frequently in skeletal muscle. We studied four ethnically distinct families affected with this apparently autosomal recessive disorder. Probands from each family were shown, by Southern blot, to have multiple mtDNA deletions in skeletal muscle. We mapped the MNGIE locus to 22q13.32-qter, distal to D22S1161, with a maximum two-point LOD score of 6.80 at locus D22S526. Cosegregation of MNGIE with a single chromosomal region in families with diverse ethnic backgrounds suggests that we have mapped an important locus for this disorder. We found no evidence to implicate three candidate genes in this region, by using direct sequence analysis for DNA helicase II and by assaying enzyme activities for arylsulfatase A and carnitine palmitoyltransferase.
线粒体神经胃肠性脑肌病（MNGIE）综合征是一种罕见的多系统疾病，临床特征为上睑下垂、进行性眼外肌麻痹、胃肠动力障碍、白质脑病、体型消瘦和肌病。实验室研究显示，骨骼肌中常存在氧化磷酸化缺陷和多个线粒体DNA缺失。我们研究了四个不同种族的家族，这些家族均患有这种明显为常染色体隐性遗传的疾病。通过Southern印迹法显示，每个家族的先证者骨骼肌中均存在多个线粒体DNA缺失。我们将MNGIE基因座定位于22q13.32 - qter，位于D22S1161的远端，在基因座D22S526处的最大两点连锁对数得分为6.80。在不同种族背景的家族中，MNGIE与单一染色体区域的共分离表明，我们已确定了该疾病的一个重要基因座。通过对DNA解旋酶II进行直接序列分析以及对芳基硫酸酯酶A和肉碱棕榈酰转移酶进行酶活性测定，我们未发现该区域的三个候选基因与该病有关的证据。
