Muller V J, Paton B C, Fietz M J
Women's and Children's Hospital, 72 King William Rd, North Adelaide, Australia.
Eur J Paediatr Neurol. 2001;5 Suppl A:197-201. doi: 10.1053/eipn.2000.0462.
The neuronal ceroid lipofuscinoses (NCLs) are a family of related genetic disorders that together are believed to affect one child in every 12,500 births in the USA. Our laboratory has developed a diagnostic service for classical late infantile neuronal ceroid lipofuscinosis (LINCL) by assay of tripeptidyl-peptidase I (TPP-I) activity using the fluorogenic peptide substrate Ala-Ala-Phe aminomethylcoumarin, followed by a screen for three mutations in the CLN2 gene. In addition, we have also begun to offer a limited diagnostic service for the juvenile (JNCL) and infantile (INCL) forms of the disease on the basis of mutation analysis of the CLN3 and CLN1 genes, respectively. Retrospective analysis of Australasian patients with a clinical suspicion of NCL has revealed that six are affected by LINCL, six by JNCL and, to date, two by INCL. Mutation analysis of our LINCL patients has shown that the three screened mutations, namely, the nonsense mutation R208X and the splice mutations IVS5-1 G > C and IVS5-1 G > A, constitute 83% of alleles.
神经元蜡样脂褐质沉积症（NCLs）是一类相关的遗传性疾病，据信在美国每12500例出生婴儿中就有1例受其影响。我们实验室通过使用荧光肽底物丙氨酸-丙氨酸-苯丙氨酸氨基甲基香豆素测定三肽基肽酶I（TPP-I）活性，随后筛查CLN2基因中的三个突变，开发了一种针对经典晚发性婴儿神经元蜡样脂褐质沉积症（LINCL）的诊断服务。此外，我们还分别基于CLN3和CLN1基因的突变分析，开始为青少年型（JNCL）和婴儿型（INCL）疾病提供有限的诊断服务。对澳大利亚临床疑似NCL的患者进行回顾性分析发现，6例患有LINCL，6例患有JNCL，迄今为止，2例患有INCL。对我们的LINCL患者进行的突变分析表明，筛查的三个突变，即无义突变R208X以及剪接突变IVS5-1 G>C和IVS5-1 G>A，占等位基因的83%。
