SPTLC2基因突变导致儿童型肌萎缩侧索硬化1例并文献复习  

SPTLC2 gene mutation leads to childhood amyotrophic lateral sclerosis: a case report and literature review

作　　者：杨洵哲[1] 丁青云[1] 刘明生[1] 管宇宙[1] 戴毅[1] 崔丽英 Yang Xunzhe;Ding Qingyun;Liu Mingsheng;Guan Yuzhou;Dai Yi;Cui Liying(Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Neuroscience Center,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院神经科,北京100730 [2]中国医学科学院北京协和医院神经科中国医学科学院神经科学中心,北京100730

出　　处：《中华神经科杂志》2023年第12期1355-1360,共6页Chinese Journal of Neurology

基　　金：中国科学院战略性先导科技专项(XDB39040100);国家重点研发计划“生育健康及妇女儿童健康保障”重点专项(2022YFC2703104)。

摘　　要：目的报道1例由SPTLC2基因突变c.778G>A(p.Glu260Lys)导致的儿童型肌萎缩侧索硬化(ALS)患者的临床特点。方法在北京协和医院神经科ALS临床数据库登记的1936例患者中,筛选携带SPTLC2基因致病突变的患者,并收集先证者的临床资料、实验室检查、神经电生理检查及基因检测结果。结果经筛选得到1例携带SPLTC2基因突变的患者,为9岁男性儿童,主因"进行性四肢无力4年余"于2022年12月收住北京协和医院神经科。体格检查发现患者舌肌明显萎缩,伴纤颤。四肢肌力下降,肌肉萎缩。双跟腱反射亢进,双踝阵挛阳性,双侧Babinski征阳性。全基因组测序结果提示SPTLC2基因存在c.778G>A(p.Glu260Lys)错义突变,未检测到其他ALS相关基因致病突变。Sanger测序验证及家系验证结果显示,患儿父亲和母亲均未携带该突变,提示为新发突变。神经传导检查未见异常,针极肌电图提示广泛神经源性损害。脑脊液及血清神经丝轻链蛋白显著升高。予L-丝氨酸口服后患者症状仍进行性加重。结论SPTLC2基因突变可导致儿童型ALS,对其潜在致病机制的研究将有助于揭示ALS的又一潜在致病通路,提供新的治疗靶点。Objective To report the clinical characteristics of a case of childhood amyotrophic lateral sclerosis(ALS)caused by SPTLC2 c.778G>A(p.Glu260Lys)mutation.Methods Whole exon sequencing or whole genome sequencing data from 1936 patients in the ALS cohort of Peking Union Medical College Hospital were screened for SPTLC2 gene mutations.Clinical data,laboratory examination,neurophysiological examination and genetic test results of the proband were collected.Results Only one 9-year-old male child with SPLTC2 gene mutation was found.He was admitted to the Department of Neurology,Peking Union Medical College Hospital in December 2022 due to"progressive limb weakness for more than 4 years".Physical examination revealed atrophy and fasciculations of the tongue.Weakness of 4 limbs,muscle atrophy,as well as bilateral hyperreflexia,clonus,and Babinski sign were present.Whole genome sequencing indicated that SPTLC2 gene had c.778G>A(p.Glu260Lys)missense mutation,and no other pathogenic mutations of ALS related genes were detected.Sanger sequencing and family verification showed that neither father nor mother carried the mutation,suggesting that it was a de novo mutation.Nerve conduction velocity test showed no abnormalities,and electromyography suggested neurogenic lesions.Neurofilament light chain in cerebrospinal fluid and serum were increased significantly.The patient′s symptoms continued worsening even after oral administration of L-serine.Conclusion SPTLC2 gene mutation can cause childhood ALS,and further study of its potential pathogenesis is helpful to uncover another potential pathway of ALS and a novel therapeutic target.

关 键 词：肌萎缩侧索硬化 儿童 丝氨酸-棕榈酰转移酶 SPTLC2基因 突变 

分 类 号：R744.8[医药卫生—神经病学与精神病学]