Ranta Susanna, Topcu Meral, Tegelberg Saara, Tan Hüseyin, Ustübütün Alp, Saatci Isil, Dufke Andreas, Enders Herbert, Pohl Keith, Alembik Yves, Mitchell Wayne A, Mole Sara E, Lehesjoki Anna-Elina
Folkhälsan Institute of Genetics and Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Finland.
Hum Mutat. 2004 Apr;23(4):300-5. doi: 10.1002/humu.20018.
Childhood-onset neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescent material in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular genetic background of the disorder, at least seven different forms are thought to exist. Northern epilepsy is a novel form of NCL so far described only in Finland, where all patients are homozygous for a missense mutation in the CLN8 gene. A variant form of late infantile NCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity among the NCL, the underlying gene (CLN7) being unknown. Recently, we reported homozygosity over the Northern epilepsy CLN8 gene region on 8p23 in four out of five Turkish vLINCL families studied. However, no common mutation in CLN8 was found in these families. We have now extended the Turkish vLINCL family panel to 18 families, of which only one is nonconsanguineous. Nine families were excluded from CLN8 by lack of homozygosity. In the remaining families, four CLN8 gene mutations were identified indicating that in a subset of patients with Turkish vLINCL, the disorder is allelic to Northern epilepsy. There is no apparent genotype-phenotype correlation among the Turkish patients with CLN8 mutations, although their phenotype is distinct from that of Finnish Northern epilepsy patients. The molecular genetic background of the Turkish vLINCL families not linked to CLN8 remains to be clarified.
儿童期起病的神经元蜡样脂褐质沉积症（NCL）是一组常染色体隐性进行性脑病，其特征是在各种组织中，尤其是在神经元中积累自发荧光物质。根据临床特征、患者的原籍国以及该疾病的分子遗传背景，人们认为至少存在七种不同的形式。北方癫痫是一种新型的NCL，迄今为止仅在芬兰被描述，该国所有患者的CLN8基因均存在错义突变的纯合子。在土耳其患者中出现的晚发性婴儿型NCL的一种变异形式（vLINCL），在NCL中被认为是一种独特的临床和遗传实体，其潜在基因（CLN7）尚不清楚。最近，我们报道在所研究的五个土耳其vLINCL家族中，有四个家族在8p23的北方癫痫CLN8基因区域存在纯合性。然而，在这些家族中未发现CLN8的常见突变。我们现在已将土耳其vLINCL家族样本扩展至18个家族，其中只有一个是非近亲家族。九个家族因缺乏纯合性而被排除在CLN8研究之外。在其余家族中，鉴定出四个CLN8基因突变，这表明在一部分土耳其vLINCL患者中，该疾病与北方癫痫是等位基因。尽管土耳其CLN8突变患者的表型与芬兰北方癫痫患者不同，但他们之间没有明显的基因型-表型相关性。与CLN8无关的土耳其vLINCL家族的分子遗传背景仍有待阐明。
