摘要
目的 对60例惊厥及发育落后且有头颅磁共振成像（MRI）改变的患儿进行基因筛查,并分析芳香基硫酸酯酶A（ARSA）基因突变者临床表现及头颅MRI表现.方法 收集患儿血样,提取基因组DNA,采用第2代测序技术对60例怀疑异染性脑白质营养不良（MLD）患儿进行基因检测,并对基因阳性患儿的基因型与临床表型及头颅MRI表现进行分析.结果 60例患儿中,15例存在基因突变,携带7种ARSA基因突变位点,其中3种与MLD相关,分别为c.1178C＞G,c.1055A＞G,c.883G＞A,而另外4个位点属于单核苷酸多态性（SNP）,1例仅携带SNP,其中14例携带致病突变.3种突变为已知致病突变,以c.1055A＞G（53.33％）、c.1178C＞ G（40.00％）多见.c.1055A＞G突变者8例,迟发型5例,其中3例晚期婴儿发作型中,1例同时携带c.1178C＞G基因突变;8例均有发育落后,脑积水1例,癫（痫）5例;c.1178C＞G突变者6例,均为晚期婴儿发作型,均有发育落后,其中癫（痫）4例,c.883G＞A突变患儿1例,为晚期婴儿发作型,其首发症状为双耳耳聋,精神发育迟滞.3种不同基因突变类型头颅MRI表现无明显差异.结论 明确了14例MLD患者的基因诊断,c.1178C＞G与c.883G＞A常为晚期婴儿发作型,c.1055A＞G为迟发型,各基因型头颅MRI表现差异无统计学意义.
Objective To detect genetic causes of seizures and developmental retardation in 60 patients with abnormal head magnetic resonance imaging（MRI） ,and to analyze the clinical manifestations and head MRI manifestations in carriers of arylsulfatase A （ARSA） gene mutation.Methods The blood samples of children and genomic DNA were collected.Sixty cases of children with suspected metachromatic leukodystrophy were tested （MLD） by using the second generation sequencing technology.The genotype and phenotype and head MRI findings were analyzed.Results Of the 60 cases of children, 15 cases with gene mutations.There were 7 kinds of ARSA gene mutations, and 3 of them, c.1178C 〉 G, c.1055A 〉 G and c.883 G 〉 A were pathogenic.The others were single nucleotide polymorphism（SNP）, which had no relationship with this disease.One of the patients carried only SNP, and 14 of them were carrying pathogenic mutation, c.1055A 〉 G （53.33%） ,c.1178C 〉 G （40.00%） were more common,and c.1055A 〉 G mutation was in 8 cases, of which 5 cases were late-onset type.One case of the 3 patients who were late infantile type was carrying c.1178C 〉 G mutation at the same time.All the eight cases had retardation.One case had hydrocephalus, and 5 cases had epilepsy.All of the 6 patients with c.1178C 〉 G were late-infantile type, and had retardation, including 4 cases of epilepsy, c.883G 〉 A mutation in 1 case,was late-infantile type,and the first symptom was binaural deafness and mental retardation.Three different types of mutations showed no significant difference in brain MRI.Conclusions There are 14 patients who were diagnosed as MLD.c.1178C 〉 G and c.883G 〉 A were late infantile type,and c.1055A 〉G was mostly late-onset type.The changes in head MRI caused by different types of ARSA gene mutations were of no significant differences in performance.
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2015年第24期1859-1862,共4页
Chinese Journal of Applied Clinical Pediatrics
关键词
异染性脑白质营养不良
突变
Metachromatic leukodystrophy
Arylsulfatase A
Mutation
