Barrientos A, Volpini V, Casademont J, Genís D, Manzanares J M, Ferrer I, Corral J, Cardellach F, Urbano-Márquez A, Estivill X, Nunes V
Departament de Medicina, Hospital Clínic i Provincial i Universitat de Barcelona, Spain.
J Clin Invest. 1996 Apr 1;97(7):1570-6. doi: 10.1172/JCI118581.
Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.
沃夫勒姆综合征是一种以常染色体隐性模式遗传的进行性神经退行性疾病。我们报告了两个携带线粒体DNA多处缺失的沃夫勒姆综合征家族。在一名患者的中枢神经系统等受影响组织中，缺失率高达85 - 90%，而在同一患者的其他组织以及家族其他成员的组织中，线粒体DNA基因组的缺失率仅为1 - 10%。最近，一个沃夫勒姆综合征基因已与4p16上的标记物相关联。在这两个家族中，疾病位点与4p16标记物之间的连锁分析在θ = 0时相对于D4S431给出了最大多点对数优势分数3.79（P<0.03）。在这些家族中，该综合征是由这个核编码基因的突变引起的，该基因与线粒体基因组发生有害相互作用。这是两个基因组参与隐性疾病的首个证据。
