Yogalingam Gouri, Pollard Tony, Gliddon Briony, Jolly Robert D, Hopwood John J
Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA, 5006, Australia.
Genomics. 2002 Feb;79(2):150-3. doi: 10.1006/geno.2002.6699.
Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomal recessive disease that occurs due to a deficiency of heparan sulfate sulfamidase (SGSH). The deficiency of SGSH results in the lysosomal accumulation and urinary excretion of the glycosaminoglycan heparan sulfate. The clinical severity of MPS IIIA is predominantly characterized by severe central nervous system degeneration. Naturally occurring MPS IIIA has recently been described in New Zealand Huntaway dogs, with similar disease progression and biochemical characteristics observed in severely affected MPS IIIA patients. Here, we identify the disease-causing mutation in the MPS IIIA Huntaway dog as 708-709insC. The frequency of the 708-709insC mutation in a sample group of 203 New Zealand Huntaway dogs was determined to be 3.8%. The identification of the 708-709insC mutation will permit the identification of heterozygous carriers as an initial step toward establishing a breeding colony of MPS IIIA dogs for the study of various therapeutic strategies targeted to the central nervous system.
ⅢA型黏多糖贮积症（MPS IIIA）是一种常染色体隐性疾病，由硫酸乙酰肝素硫酸酯酶（SGSH）缺乏引起。SGSH缺乏导致糖胺聚糖硫酸乙酰肝素在溶酶体中蓄积并经尿液排泄。MPS IIIA的临床严重程度主要表现为严重的中枢神经系统退化。最近在新西兰汉塔威犬中发现了自然发生的MPS IIIA，在严重受影响的MPS IIIA患者中观察到了类似的疾病进展和生化特征。在此，我们确定MPS IIIA汉塔威犬的致病突变是708 - 709insC。在203只新西兰汉塔威犬的样本组中，708 - 709insC突变的频率被确定为3.8%。708 - 709insC突变的鉴定将有助于识别杂合携带者，这是建立MPS IIIA犬繁殖群体以研究针对中枢神经系统的各种治疗策略的第一步。
