基于基因检测诊断晚婴型神经元蜡样脂褐质沉积症1例

One case of late infantile neuronal ceroid lipofuscinoses diagnosed by gene detection

对1例晚婴型神经元蜡样脂褐质沉积症(LINCL)患儿进行临床诊断和遗传学分析。该患儿TPP1存在c.1424C>T(p.Ser475Leu)和c.962A>G(p.His321Arg)复合杂合突变,分别遗传其父亲和母亲,突变致病性分析均为有害和致病,蛋白序列同源性比对中同源区域均为高度保守。患儿可能是由TPP1复合杂合突变导致的晚婴型神经元蜡样脂褐质沉积症,其中c.962A>G(p.His321Arg)位点突变尚未见报道,新突变基因的发现扩大了该基因的突变谱,为阐明LINCL遗传机制提供线索和方向。全外显子组测序技术(WES)可作为发现LINCL的诊断手段,可为临床表型复杂的疾病确诊提供依据。

To clinically diagnose and genetically analyze one case of late infantile neuronal ceroid lipofuscinoses(LINCL).The patient had carried compound heterozygous mutations of gene TPP1,namely c.1424C>T(p.Ser475Leu)and c.962A>G(p.His321Arg),which were inherited from his father and mother,respectively.The analysis of mutation pathogenicity showed that the mutations were both deleterious and pathogenic,and the homologous comparison of protein sequences indicated that the homologous region was highly conservative.The LINCL may be caused by TPP1 compound heterozygous mutations.The site mutation of c.962A>G(p.His321arg)has not been reported.The discovery of the new mutated gene expanded the mutated spectrum of the gene and provided clues and directions for elucidating the genetic mechanism of LINCL.WES can be used as a diagnostic method to detect LINCL,and it can provide a basis for the diagnosis of diseases with complex clinical phenotypes.