Genotype-phenotype correlation and natural history analyses in a Chinese cohort with pelizaeus-merzbacher disease

Orphanet J Rare Dis. 2022 Mar 28;17(1):137. doi: 10.1186/s13023-022-02267-z.


Background: The natural history and genotype-phenotype correlation of Pelizaeus-Merzbacher disease (PMD) of Chinese patients has been rarely reported.

Method: Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype-phenotype correlations were analyzed.

Result: A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age.

Conclusion: PMD patients have early disease onset with nystagmus and hypotonia followed by decreased nystagmus and movement disorders, such as spasticit. Patients with PLP1 duplication were more likely to be categorized into the mild group, whereas patients with point mutations were more likely to be categorized into the severe group.

Keywords: Chinese cohort; Genotype; Natural history; Pelizaeus–merzbacher disease; Phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Follow-Up Studies
  • Genetic Association Studies
  • Humans
  • Myelin Proteolipid Protein / genetics
  • Pelizaeus-Merzbacher Disease* / diagnosis
  • Pelizaeus-Merzbacher Disease* / genetics


  • Myelin Proteolipid Protein