TBCD基因变异致微管蛋白病伴非典型脊髓性肌萎缩症1例报告
TBCD gene variation causing tubulinopathy with atypical spinal muscular atrophy: one case report
Received date: 2021-08-03
Online published: 2022-11-10
微管蛋白病为一种少见的由TBCD变异所致的常染色体隐性遗传性疾病，临床特点为早发进行性脑病。患儿，男，11月龄。8月龄时出现热性惊厥，为局灶性发作，初期洗澡或发热后出现，后期无热时也有抽搐发作。患病以来精神运动进行性倒退，11月龄时四肢活动渐减少。肌电图示广泛性神经源性损害。头颅MRI示脑沟增宽，胼胝体变薄，脑发育不良。全外显子组基因测序提示患儿携带TBCD基因复合杂合变异：第2外显子c.230A>G(p.H77R)杂合错义变异和第13外显子c.1306C>T(p.R436*,757)杂合终止变异，此两位点变异国内外尚未见报道。其父携带c.230A>G突变，其母携带c.1306C>T突变。最终患儿确诊微管蛋白病伴非典型脊髓性肌萎缩症（SMA）。1岁4个月时随访患儿共服用4种抗癫痫药，抽搐减少。该例表型伴非典型SMA病例丰富了微管蛋白病的临床表型谱，基因检测发现的1个新发终止变异和1个新发错义变异扩大了TBCD基因变异谱。
周露露 , 丁乐 , 郑帼 . TBCD基因变异致微管蛋白病伴非典型脊髓性肌萎缩症1例报告[J]. 临床儿科杂志, 2022 , 40(11) : 854 -857 . DOI: 10.12372/jcp.2022.21e1128
Tubulinopathy is a rare autosomal recessive hereditary disease caused by TBCD variation and characterized by early-onset progressive encephalopathy. The patient was a boy aged 11 months. At the age of 8 months, he had a febrile convulsion which was a focal seizure. It appeared after bathing or fever in his early stage, and convulsions occurred at any time in the later stage. Since the onset of the disease, the psychomotor function has been progressively retrogressed. At the age of 11 months, the activity of his limbs gradually decreased, and the results of electromyography showed extensive neurogenic damage. The cranial magnetic resonance imaging showed the widened sulcus, thinned corpus callosum and cerebral dysplasia. The results of whole exome gene sequencing indicated that the child carried complex heterozygous variations of TBCD gene: a heterozygous missense variation of c.230A>G (p.H77R) in exon 2 and a heterozygous termination variation of c.1306C>T (p.R436*, 757) in exon 13. The two variants have not been reported. The father carried c.230A>G variation, and the mother carried c.1306C>T variation. Finally, the child was diagnosed with tubulinopathy with atypical spinal muscular atrophy (SMA). At the age of 1 year and 4 months, the child was treated with four antiepileptic drugs and had fewer convulsions. The phenotype in this case was accompanied by atypical SMA, which enriched the clinical phenotypes spectrum of the disease. A new termination mutation and a new missense mutation detected by genetic testing enlarged the TBCD gene variation spectrum.
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