Barrientos A, Casademont J, Saiz A, Cardellach F, Volpini V, Solans A, Tolosa E, Urbano-Marquez A, Estivill X, Nunes V
Departament de Medicina, Hospital Clínic i Provincial i Universitat de Barcelona, Spain.
Am J Hum Genet. 1996 May;58(5):963-70.
Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and approximately 5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level.
沃夫勒姆综合征（MIM 222300）的特征为视神经萎缩、糖尿病、尿崩症、神经感觉性听力丧失、泌尿系统异常以及神经功能障碍。在功能或胚胎学上不相关的组织和器官中出现的临床表现关联提示了线粒体参与该疾病的可能性，这在两例散发病例中得到了证实。尽管如此，家族研究提示其遗传方式为常染色体隐性遗传，并且最近的数据表明与人类4号染色体短臂上的标记存在连锁关系。本文报道的患者及其父母和未患病的姐姐，其线粒体DNA（mtDNA）中均存在一个8.5 kb的异质性缺失。该缺失在患者淋巴细胞的线粒体基因组中占23%，在其家庭成员所研究的组织中约占5%。患者体内该缺失的比例高于其未患病父母，这提示在线粒体水平起作用的一个核基因存在推定缺陷。
