Clinical and genetic phenotypes of a patient with POLR3B gene-related hypomyelinating leukodystrophy and hypogonadism
10.3760/cma.j.cn113694-20200331-00229
- VernacularTitle:POLR3B基因突变相关低髓鞘化脑白质营养不良伴性腺功能减退一例表型及基因突变分析
- Author:
Linwei ZHANG
1
;
Dantao PENG
Author Information
1. 中日友好医院神经科，北京 100029
- From:
Chinese Journal of Neurology
2020;53(10):746-752
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of POLR3B gene related autosomal recessive cerebellar ataxia with hypogonadism.Methods:A female proband from a Chinese non-consanguineous family was admitted to Department of Neurology, China-Japan Friendship Hospital in March 2016, performed detailed physical and auxiliary examinations and excluded acquired causes of cerebellar ataxia. Genomic DNA was extracted from peripheral blood of the proband and conducted whole exome sequencing (WES) and verified in her asymptomatic parents. Potential pathogenic variants were validated by Sanger sequencing.Results:The proband exhibited progressive unsteady walk, cognitive impairment, dysarthria and dysphagia, dystonia, congenital cataract, hypogonadism as well as delayed puberty, amenorrhea and short stature and was effectively treated by hormone therapy. Magnetic resonance imaging of her brain showed diffused hypomyelination of white matter, relatively sparing the thalamus, globus pallidus, and optic radiations, as well as cerebellar atrophy and thin corpus callosum. X ray of her chest revealed thoraco-lumbar scoliosis. WES identified compound heterozygous mutations c.479A>C (p. E160A) and c.2657G>C (p.R886T) of POLR3B gene in this patient, and they were novel mutations, which were respectively inherited from her father and mother validated by Sanger sequencing. Bioinformatic analysis predicted these two mutations were pathogenic.Conclusion:The clinical and imaging features of POLR3B-associated leukodystrophy with hypogonadism were considerably evident, diagnosis and treatment of which should be conducted as early as possible.
