Abstract: Objective　To explore the clinical manifestation of Pelizaeus-Merzbacher disease (PMD) and the mutation of protein lipoprotein 1 (PLP1) gene. Method　Clinical data and genetic analysis of PMD in 2 probands and their family members were collected. Results　Both of the two probands were male and had developmental retardation from childhood, and nystagmus was found shortly after birth. Paroxysmal spasm with progressive emaciation was developed in proband 1 at 2 years of age. Brain magnetic resonance imaging (MRI) of both probands showed white matter dysplasia and myelin sheath dysplasia. Each of the 2 probands had an elder brother with similar manifestations. Gene sequencing results showed that proband 1 had a hemizygous mutation, c. 137T > c (p.eu46pro), in exon 2 of the PLP1 gene and the proband 2 had a hemizygous mutation, c. 62C > T (p.ala21val), in exon 2 of the PLP1 gene. The mothers of the two probands had normal phenotype, but both of them had the same heterozygous variation as the probands; and the elder brother of both probands had the same hemizygote mutation as the probands. The mutation sites of 2 probands were not reported and confirmed as pathogenic sites by pathogenicity analysis of ACMG. Conclusion　The mutation and genetic characteristics of PLP1 gene in two families were identified. The mutation site was not included in ClinVar database, and the findings enriched the pathogenic mutation spectrum of PLP1.

Key words: Pelizaeus-Merzbacher disease;　proteolipid protein 1;　gene mutation