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
10.3760/cma.j.issn.0578-1426.2017.06.009
- VernacularTitle:β微管蛋白4A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一例并文献复习
- Author:
Ying DU
;
Chuan LI
;
Jun GUO
;
Peng GUO
;
Zhuyi LI
;
Wei ZHANG
- Keywords:
Tubulin beta 4A;
Mutation;
Hypomyelinating leukodystrophies;
Atrophy of the basal ganglia and cerebellum;
Neuroimaging
- From:
Chinese Journal of Internal Medicine
2017;56(6):433-437
- CountryChina
- Language:Chinese
-
Abstract:
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 T2-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 18F-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.
