[A report of atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum caused by a de novo mutation in tubulin beta 4A (TUBB4A) gene and literature review].

Objective: To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation. Methods: We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC. Results: The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment. MRI showed regional blurring of slight high signal on T(2)-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus. Compared with normal subjects of the same age and gender, hypometabolism was found by (18)F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient. Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c. 70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software. Conclusions: The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features. Genetic testing for pathogenic mutation in TUBB4A gene is a key for the diagnosis of H-ABC.目的： 探讨β微管蛋白4A (TUBB4A)基因新突变致非典型伴基底节及小脑萎缩的低髓鞘化脑白质营养不良(H－ABC)的临床、影像、基因学特征及发病机制，以提高对该病认识。 方法： 回顾性分析1例明确诊断的非典型H－ABC患者的临床表现、神经心理评估、神经影像及基因检测结果，总结其临床、神经影像学及基因学特点。 结果： 本例非典型H－ABC患者主要以进行性痉挛性瘫痪、轻度小脑共济失调和轻度认知功能障碍为主要临床症状。神经影像检查显示，双侧中脑腹侧、内囊后肢、侧脑室后角旁及半卵圆中心对称分布斑片状稍长T(2)高信号影，及液体衰减反转恢复(FLAIR)序列呈稍高信号影，双侧尾壳核及小脑半球形态及信号未见异常。(18)F－脱氧葡萄糖－正电子发射断层扫描((18)F－FDG－PET)检查显示，患者与相同年龄和性别的正常者相比，脑干、小脑及尾壳核区域(18)F－FDG代谢水平明显降低。基因检测发现，在TUBB4A基因外显子区域有一处错义杂合突变位点c.70G>A(鸟嘌呤→腺嘌呤)，导致氨基酸改变(p.G24R，甘氨酸>精氨酸)，人类基因突变数据库(HGMDpro)中未见报道；患者父母均未携带该突变；突变致病性预测软件分析显示其为有害突变，表明该处错义杂合突变为新生致病性突变。 结论：TUBB4A基因突变的多样性导致不同程度的皮层下白质、小脑及尾壳核功能性和/或结构性损伤，进而造成H－ABC的临床症状和神经影像呈非典型表现，TUBB4A基因检测分析有助于明确H－ABC诊断。.