晚期婴儿型神经元蜡样质脂褐素沉积病患者临床特点和基因改变

Clinical and genetic studies of late-infantile neuronal ceroid lipofuscinosis

目的总结临床病理诊断为晚期婴儿型神经元蜡样质脂褐素沉积病(LINCL)患者的临床特点和基因改变。方法总结分析9例LINCL患者(其中3例为文献报道的患者)的临床特点,并对其中4例患者进行CLN2基因检测。结果癫痫是我国LINCL患者最主要的首发临床症状,其发作表现形式多样。CLN2基因检查结果显示,在两例患者分别发现位于第3内含子的IVS3-1G→A剪接突变和第6外显子的G217V杂合突变以及第13外显子的S538Y纯合突变,上述突变均为文献尚未报道过的新突变,在50名健康人中未发现这些基因突变。另两例患者CLN2基因检查正常。结论我国LINCL患者癫痫发作具有多种表现形式,肌阵挛癫痫不常见。我国CLN2基因的突变类型与其他国家或地区可能不同,也可能存在新的基因。

Objective To report the clinical and genetic studies of Chinese patients with late-infantile neuronal ceroid lipofuscinosis （LINCL）. Methods To summarize the clinical characteristics o{ 9 Chinese LINCL patients （including 3 cases reported previously）. CLN2 gene was examined in 4 patients. Results The foremost symptom of Chinese LINCL patients is seizure with various patterns. One splicing mutation and two missense mutations were identified in the following two patients： one patient carrying a compound heterozygous mutation of a IVS3-1G→A mutation in intron 3 and a G217V mutation in exon 6, another proband carrying a homozygous mutation of S538Y in exon 13. All of these mutations, which lead to LINCL, are novel. The CLN2 genes of the other two patients were not found mutation. Conclusions The main pattern of seizure is the tonic-clonic and the complexity-partial, while the myoclonic is not common. The genetic abnormalities of CLN2 in Chinese patients are different from the patients of other nationalities and other mutant genes maybe existence.