Duplication of proteolipid protein gene: a possible major cause of Pelizaeus-Merzbacher disease.

The classic form of Pelizaeus-Merzbacher disease is a rare X-linked dysmyelinating disorder of the central nervous system in which mutations of the proteolipid protein gene have been reported since 1989. However, mutations in the proteolipid protein gene have been identified in only 10 to 25% of all cases of Pelizaeus-Merzbacher disease, which suggests that other genetic aberrations may be present. Recently, proteolipid protein gene overdosage was discovered to cause Pelizaeus-Merzbacher disease. By using comparative multiplex polymerase chain reaction and restriction fragment length polymorphism analysis, we confirmed the proteolipid protein gene duplication as the cause of Pelizaeus-Merzbacher disease in 4 patients from 3 Chinese families with Pelizaeus-Merzbacher disease with no detectable exonic mutations. These results support the hypothesis that proteolipid protein gene duplication may be a major cause of Pelizaeus-Merzbacher disease in all ethnic groups and also suggest that the molecular diagnosis of Pelizaeus-Merzbacher disease should therefore include duplication analysis of proteolipid protein gene.