Open AccessHypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients
Author(s) -
Haoran Ji,
Dongxiao Li,
Ye Wu,
Quanli Zhang,
Qing Gu,
Han Xie,
Taoyun Ji,
Hong Wang,
Lu Zhao,
Haijuan Zhao,
Yanling Yang,
Hongchun Feng,
Hui Xiong,
Jinhua Ji,
Zhixian Yang,
Liping Kou,
Ming Li,
Xinhua Bao,
Xingzhi Chang,
Yuehua Zhang,
Li Li,
Huijuan Li,
Zhengping Niu,
Xiru Wu,
Jiangxi Xiao,
Yuwu Jiang,
Jingmin Wang
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0188869
Subject(s) - leukodystrophy , biology , exome sequencing , population , genetics , sanger sequencing , ataxia , pathology , medicine , mutation , disease , gene , environmental health , neuroscience
Objective Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population. Methods 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing. Results Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1 , GJC2 , TUBB4A , GLB1 , HEXA , HEXB , ERCC2 , POLR3A , and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively. Significance This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.