Willems P J, Darby J K, DiCioccio R A, Nakashima P, Eng C, Kretz K A, Cavalli-Sforza L L, Shooter E M, O'Brien J S
Department of Neurosciences, University of California, San Diego 92093.
Am J Hum Genet. 1988 Nov;43(5):756-63.
Fucosidosis is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration and mental retardation. The disease results from deficient activity of alpha-L-fucosidase (E.C.3.2.1.51), a lysosomal enzyme that hydrolyzes fucose from fucoglycoconjugates. In an attempt to identify the mutation(s) that result(s) in fucosidosis, we performed Southern blot analysis of the structural gene encoding alpha-L-fucosidase (FUCA 1) in 23 patients affected with fucosidosis. In five patients Southern blot analysis showed obliteration of an EcoRI restriction site in the open reading frame of FUCA 1 encoding mature alpha-L-fucosidase. This abnormality was not observed in 80 controls, and it may be the basic defect responsible for fucosidosis in these patients. Both patients with the severe type I form of fucosidosis and patients with the less severe type II were shown to be homozygous for this presumed mutation. In the remaining 18 patients the EcoRI site obliteration, major-gene deletions, or insertions were not detected. This suggests that at least two different mutations are involved in fucosidosis. The heterogeneity found at the DNA level was not present at the protein level, as all fucosidosis patients investigated had low fucosidase protein (less than 6% of normal) and negligible fucosidase activity in fibroblasts and lymphoblastoid cell lines.
岩藻糖苷贮积症是一种常染色体隐性溶酶体贮积病，其特征为进行性神经功能衰退和智力迟钝。该疾病是由于α-L-岩藻糖苷酶（E.C.3.2.1.51）活性不足所致，α-L-岩藻糖苷酶是一种溶酶体酶，可从岩藻糖糖缀合物中水解岩藻糖。为了确定导致岩藻糖苷贮积症的突变，我们对23例岩藻糖苷贮积症患者中编码α-L-岩藻糖苷酶（FUCA 1）的结构基因进行了Southern印迹分析。在5例患者中，Southern印迹分析显示在编码成熟α-L-岩藻糖苷酶的FUCA 1开放阅读框中一个EcoRI限制性位点消失。在80名对照中未观察到这种异常，它可能是这些患者岩藻糖苷贮积症的基本缺陷。I型严重岩藻糖苷贮积症患者和II型较轻患者均显示为该假定突变的纯合子。在其余18例患者中未检测到EcoRI位点消失、主要基因缺失或插入。这表明岩藻糖苷贮积症至少涉及两种不同的突变。在DNA水平发现的异质性在蛋白质水平并不存在，因为所有接受调查的岩藻糖苷贮积症患者的岩藻糖苷酶蛋白含量都很低（低于正常水平的6%），并且在成纤维细胞和淋巴母细胞系中的岩藻糖苷酶活性可忽略不计。
