摘要
目的探讨B3GALNT2基因突变致先天性肌营养不良的临床特点。方法收集2019年1-6月河北省儿童医院收治的B3GALNT2基因突变致先天性肌营养不良亚型α-抗肌萎缩相关糖蛋白病(α-dystroglycanopathy,α-DGP)患儿的临床资料,并检索相关文献对其致病特点进行临床分析。结果共有2例B3GALNT基因突变致α-DGP患儿,均为复合杂合突变。1例等位基因突变位点为c.1068dup T(p.D357D358delinsX)和c.40G>C(p.G14R),另1例等位基因突变位点为c.261-2A>G(Splicing)和c.979G>A(p.D327N)。文献检索到19例B3GALNT2基因突变致α-DGP患者。总结分析其特点:①神经系统均受累,常见临床症状为认知、运动发育障碍(100%),癫痫发作(52.6%),肌张力低(64.3%);②头颅MRI异常可表现为脑室周围白质病变(81.3%),神经元移行障碍(68.8%),脑干和/或小脑发育不良(56.3%),小脑皮层囊肿(50%),重度脑积水(31.25%)等;③肌受累患者可达63.2%,肌酶升高多为300~1740U/L,重症者可更高;④眼受累患者占28.6%,常见症状为视神经萎缩、眼裂畸形,严重者可见青光眼、白内障,甚者失明;⑤推测该基因截短突变且突变位置靠前者症状较重,错义突变往往症状较轻,突变位点c.979G>A(p.D327N)及c.822823dup(p.I276Lfs*26)可能为热点突变;⑥该基因突变部分症状有自愈倾向。结论 B3GALNT2基因应作为婴幼儿期α-DGP、智力运动发育落后、癫痫及多种脑发育畸形等表现的候选筛查基因之一。
Objective To explore the clinical features of congenital muscular dystrophy caused by mutation of B3GALNT2 gene. Method The clinical data of children with α-DGP caused by B3GALNT2 gene mutation admitted to our hospital from January 2019 to June 2019 were collected, and related literature was searched for clinical analysis of their pathogenic characteristics. Result 2 cases of α-DGP caused by B3GALNT gene mutation were collected, both of which were compound heterozygous mutations.1 case of the allelic mutations was c.1068 dup T(p.D357D358 delinsX) and c.40 G> C(p.G14 R), another case of the allelic mutations was c.261-2 A> G(Splicing) and c.979 G> A(p.D327 N). B3GALNT2 gene mutation causes α-DGP: ①100% of the nervous system is involved, the common clinical symptoms are cognitive and motor development disorders(100%), seizures(52.6%), and low muscle tone(64.3%);②abnormal brain MRI can be manifested as white matter lesions around the ventricle(81.3%), neuronal migration disorders(68.8%), brain stem and/or cerebellar dysplasia(56.3%), cerebellar cortical cysts(50%), severe hydrocephalus(31.25)%;③patients with muscle involvement account for 63.2%, and the increase in muscle enzymes is mostly between 300-1740 U/L, which can be higher in severe cases;④eye-affected patients account for 28.6%, common symptoms are optic atrophy, eye fissure deformity, glaucoma, cataract, and even blindness in severe cases;⑤ it is speculated that the truncated mutation of the gene and the position of the mutation is more severe, and the missense mutation is often milder, mutation sites c.979 G> A(p.D327 N) and c.822823 dup(p.I276 Lfs * 26) may be hot spot mutations;⑥some symptoms of this gene have a tendency to heal. Conclusion B3 GALNT2 gene should be used as one of the candidate screening genes for infantile α-DGP, mental and motor developmental lag, epilepsy, and various brain developmental deformities.
作者
吴文娟
郝京霞
李宝广
Wu Wenjuan;Hao Jingxia;Li Baoguang(Department of Neurology,Hebei Children’s Hospital,Hebei Shijiazhuang 050031,China;Department of Cardiology,Hebei Children’s Hospital,Hebei Shijiazhuang 050031,China)
出处
《中国医刊》
CAS
2020年第8期870-874,共5页
Chinese Journal of Medicine
基金
河北省医学科学研究课题计划(20190788)。
