| 康庆云，廖红梅，杨赛，陈波，杨理明.ASAH1基因突变致脊髓性肌萎缩症2例并文献复习[J].神经损伤功能重建,2020,15(10):575-578 |
| ASAH1基因突变致脊髓性肌萎缩症2例并文献复习 |
| ASAH1 Gene Mutation Causing Spinal Muscular Atrophy: 2 Cases Report and Literature Re⁃view |
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| DOI： |
| 中文关键词: 脊髓性肌萎缩症 基因突变 ASAH1基因 |
| 英文关键词: spinal muscular atrophy genetic mutations ASAH1 gene |
| 基金项目:湖南省卫生计生
委 科 研 课 题（No.
B20180528） |
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| 摘要点击次数: 2507 |
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| 中文摘要: |
| 目的：总结2例ASAH1基因突变致脊髓性肌萎缩症（SMA）患儿临床特点及遗传学特征，并进行文献
复习，以提高对该病的认识。方法：报道我院2例确诊为ASAH1基因突变相关性SMA，并对至今报道的14
例ASAH1基因突变相关性SMA病例进行汇总分析。结果：2例患儿系姐弟。患儿1，女，13岁9月，早期生
长发育里程碑基本正常，8岁左右出现行走姿势异常，缓慢进展，渐出现爬楼困难，跑跳困难；患儿2，男，9岁 4月，1岁2个月时能独立行走，6岁左右出现肢体乏力，跑步姿势异常，缓慢进展。全外显子组基因测序结
果示2例患儿均携带ASAH1基因复合杂合突变，第13内含子c.1098+1G>T杂合突变，为剪接突变，此位点
为国际上已报道的致病性突变；第3内含子c.216+11A>G杂合突变，此位点为国际上尚未报道的新突变。2
例患儿自起病以来，运动功能进行性倒退，病程中均未出现癫痫发作，智力基本正常。搜索既往报道，至
2019年9月，国内外共报道14例ASAH1基因突变相关性SMA。14例患者中，2例仅有SMA症状，12例既
有SMA又有进行性肌阵挛性癫痫（PME）；患者多以肌无力起病，一般5岁左右起病，病程中出现进行性肌
阵挛癫痫，多于 7～12 岁出现癫痫发作，震颤、反复肺炎、吞咽困难等症状也常在病程中出现。共发现
ASAH1基因9种不同的突变位点，其中c.125C>T为最常见突变位点，均以常染色体隐性遗传方式发病。所
有病例早期发育里程碑大致正常，病程中患儿认知功能无明显损害，文献报道时已有４例患儿青少年期死
亡。结论：ASAH1基因突变相关性SMA为一种少见的进行性常染色体隐性遗传病，由ASAH1基因突变所
致，ASAH1基因突变常引起SMA-PME表型，ASAH1基因突变亦可仅引起脊髓性肌萎缩症，而不出现进行
性肌阵挛癫痫。本例携带１个文献报道的剪切突变及１个未报道的内含子区点突变，为中国首次报道的
ASAH1基因突变仅有脊髓性肌萎缩症表型而不出现进行性肌阵挛癫痫病例。 |
| 英文摘要: |
| To study the clinical and genetic characteristics of 2 Chinese children with spinal muscular atrophy (SMA) caused by mutations in the ASAH1 gene and review relevant literature. Methods: The clinical and genetic data of 2 patients diagnosed at our hospital with SMA caused by the ASAH1 gene mutation was
analyzed．In addition, 14 reported cases of SMA associated with the ASAH1 gene mutation were summarized
and analyzed. Results：The 2 patients are siblings. Patient 1 was a girl aged 13 years and 9 months with generally normal early developmental milestones. At 8 years old, she started to show slowly progressive difficulty in
walking, stair-climbing, running and jumping. Patient 2 was a boy aged 9 years and 4 months; he was able to
walk independently at 1 year 2 months. Around age 6, he began showing slowly progressive limb weakness and
abnormal running posture. Whole exome sequencing revealed that both patients harbored compound heterozygous mutations in the ASAH1 gene; c.1098+1G>T in intron 13 is a splicing mutation, and this site had been internationally reported as a pathogenic mutation; c.216+11A>G in intron 3 had never been internationally reported before. Since the onset of disease, the 2 patients experienced a progressive regression in motor function. The
patients suffered no seizures during the course of the disease, and their intelligence remained basically normal.
As of September 2019, a total of 14 children with ASAH1 mutation-related SMA had been reported at home and
abroad; among them, 2 patients had only SMA symptoms and 12 both SMA and progressive myoclonic epilepsy
(PME). In these 14 patients, disease generally started with muscular weakness around age 5; seizures occur
around 7-12 years old; and tremors, recurrent pneumonia, dysphagia, and other symptoms often appeared
through the course of the disease. A total of 9 mutations of the ASAH1 gene were found, with the most prevalent
being c.125C>T. The mode of inheritance was autosomal recessive in all patients. In all cases, early developmental milestones were normal, and cognitive function showed no significant impairment throughout the disease
course. At the time of this report, 4 patients have died in adolescence. Conclusion：ASAH1 gene mutation-associated SMA is a rare, progressive autosomal recessive hereditary disease caused by the ASAH1 gene mutation.
Mutations in the ASAH1 gene often produce SMA-PME phenotypes and may also cause only spinal muscular atrophy without the presence of progressive myoclonic epilepsy. This case provides 1 previously reported splicing mutation and 1 unreported intron point mutation; this is the first reported case of ASAH1 gene mutation in China that resulted in the SMA-only phenotype without the presence of
PME. |
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