Ju Weina, Wronska Anetta, Moroziewicz Dorota N, Zhong Rocksheng, Wisniewski Natalia, Jurkiewicz Anna, Fiory Michael, Wisniewski Krystyna E, Johnston Lance, Brown W Ted, Zhong Nanbert
SCL-Molecular Neurogenetic Diagnostic Laboratory, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Feb 18;38(1):41-8.
Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL).
Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles.
The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.
Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.
对517例临床诊断为经典型神经元蜡样脂褐质沉积症（NCL）的患者进行基因型-表型关联研究。
分析CLN1 - 3基因位点的发病年龄、初始神经症状及电子显微镜（EM）特征。
导致临床评估的最常见初始症状在NCL1中为发育迟缓（30%），在NCL2中为癫痫发作（42.4%），在NCL3中为视力问题（53.5%）。82%的NCL1病例具有嗜锇颗粒沉积（GROD）或含混合GROD的EM特征；94%的NCL2病例具有曲线样（CV）或含混合CV的特征；91%的NCL3病例具有指纹样（FP）或含混合FP的特征。约三分之一的NCL病例存在混合型EM特征。特定CLN基因内的DNA突变与NCL表型进一步相关。在NCL2中，癫痫发作与CLN2的常见突变523G>A和636C>T相关，但在NCL1中与CLN基因的常见突变223G>A和451C>T无关。视力丧失是NCL3所有类型突变的初始症状。令人惊讶的是，我们的数据显示，51.3%的NCL1（婴儿型）病例、19.7%的NCL2（晚婴儿型）病例和42.8%的NCL3（青少年型）病例的发病年龄不典型。
我们的数据提供了关于经典儿童NCL临床识别的总体情况。这可能有助于通过其特征性临床特征对NCL1 - 3进行预测和基因鉴定。
