Mucolipidosis IV consists of one complementation group

Mucolipidosis IV (MLIV) is an autosomal recessive disorder of unknown etiology characterized by severe visual impairment and psychomotor retardation. Recently, there has been considerable interest in positional cloning of the MLIV gene. It is unknown whether MLIV is a genetically homogenous disorder. In this paper, we present experiments that determined whether the MLIV phenotype in fibroblasts could be corrected by fusing normal cells to MLIV cells and fusing fibroblasts from pairs of patients. All of our MLIV patients fulfilled several diagnostic criteria that we developed. In addition, we found high sensitivity to chloroquine in cultured fibroblasts from MLIV patients. We found that normal cells corrected the MLIV phenotype. Fusion products of normal and MLIV fibroblasts, but not MLIV fibroblasts themselves, were relatively protected against chloroquine selection. In addition, 74% of the normal-to-patient fusion products had reduced levels or total loss of MLIV characteristic autofluorescence. However, there was no complementation of the phenotype in fibroblast cultures from any of our MLIV patients, including those of non-Jewish ancestry. In fusion products of MLIV cultures from 24 patients, 90–100% of the cells remained autofluorescent. These results indicate that all of our known MLIV patients, regardless of ancestry or severity of the developmental defect, have a single mutated gene.

粘多糖脂贮积症IV型（Mucolipidosis IV, MLIV）是一种病因未明的常染色体隐性遗传病，以严重视力损害和精神运动发育迟缓为特征。近年来，学界对MLIV致病基因的定位克隆研究产生了浓厚兴趣。目前尚不清楚MLIV是否为遗传均质性疾病。本文中，我们开展了相关实验，以验证正常细胞与MLIV患者成纤维细胞融合、以及不同患者成纤维细胞两两融合后，能否纠正MLIV的表型。我们的所有MLIV患者均符合我们制定的多项诊断标准。此外，我们发现MLIV患者的培养成纤维细胞对氯喹具有高度敏感性。我们观察到，正常细胞可纠正MLIV的表型：正常与MLIV成纤维细胞的融合产物（而非MLIV成纤维细胞本身）可相对抵御氯喹的筛选作用。同时，74%的正常-患者融合产物的MLIV特征性自发荧光水平降低或完全消失。然而，在我们纳入的所有MLIV患者（包括非犹太裔患者）的成纤维细胞培养中，均未出现表型互补现象。在24例MLIV患者的成纤维细胞融合产物中，90%~100%的细胞仍呈现自发荧光。上述结果表明，我们所研究的所有已知MLIV患者，无论其种族血统或发育缺陷严重程度如何，均携带单一突变基因。