神经元蜡样质脂褐质沉积病(NCL)的基因型与表型相关性研究(英文)

查看全文 作　　者：Weina [1,2]JU;Anetta [1,2]WRONSKA;Dorota N. [1,2]MOROZIEWICZ;Rocksheng [1,6]ZHONG;Natalia [8]WISNIEWSKI;Anna [1,2]JURKIEWICZ;Michael [4]FIORY;Krystyna E. [3,4]WISNIEWSKI;Lance [7]JOHNSTON;W. Ted [2]BROWN;Nanbert [1,2,5,8]ZHONG 机构地区：[1]SCL-MolecularNeurogeneticDiagnosticLaboratory;[2]DepartmentofHumanGenetics;[3]DepartmentofPathologicalNeurobiology;[4]DepartmentofInfantDevelopment,NewYorkStateInstituteforBasicResearchinDevelopmentalDisabilities,StatenIsland,NY;[5]DepartmentofNeurology,SUNYDownstateHealthCenter,Brooklyn,NY;[6]SummerStudent,HarvardUniversity,Boston,MA;[7]BattenDiseaseSupportandResearchAssociation,Columbus,OH;[8]北京大学医学遗传中心、北京大学基础医学院医学遗传学系,北京100083 出　　处：《北京大学学报(医学版)》索引2006年第38卷第1期,共8页 基　　金：SupportedbytheNewYorkStateOfficeofMentalRetardationandDevelopmentalDisabilities(OMRDD),theBattenDiseaseSupportandResearchFoundation(BDSRA),theChildren’sBrainDiseasesFoundation(CBDF),NIH/NINDS(R21NS042806)andtheNationalNaturalSciencesFoundationofChina(30228019)国家自然科学基金 摘　　要：Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: 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.Conclusion: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. 关 键 词：神经元蜡样质脂褐质沉积病 基因型 表型 基因 CLN 突变