Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients

PLoS One. 2018 Feb 16;13(2):e0188869. doi: 10.1371/journal.pone.0188869. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China / epidemiology
  • Chromosome Banding
  • Female
  • Genetic Heterogeneity*
  • Hereditary Central Nervous System Demyelinating Diseases / diagnostic imaging
  • Hereditary Central Nervous System Demyelinating Diseases / epidemiology*
  • Hereditary Central Nervous System Demyelinating Diseases / genetics
  • Hereditary Central Nervous System Demyelinating Diseases / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Karyotyping
  • Magnetic Resonance Imaging
  • Male

Grants and funding

This study was funded by the Ministry of Science and Technology of the People's Republic of China (2012CB944602, 2012BAI09B04; http://www.most.gov.cn/), National Natural Science Foundation of China (81271257, 81200873; http://www.nsfc.gov.cn/), Beijing Natural Science Foundation (7132208; http://bjnsf.bjkw.gov.cn/), and Beijing Municipal Science & Technology Commission (BZ0317; http://www.bjkw.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.