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 dy smyelinating disorder of the central nervous system in which mutations of the proteolipid protein gene have been reported since 1989. Howeve r, mutations in the proteolipid protein gene have been identified in o nly 10 to 25% of all cases of Pelizaeus-Merzbacher disease, which sugg ests that other genetic aberrations may be present, Recently, proteoli pid protein gene overdosage was discovered to cause Pelizaeus-Merzbach er disease, By using comparative multiplex polymerase chain reaction a nd restriction fragment length polymorphism analysis, we confirmed the proteolipid protein gene duplication as the cause of Pelizaeus-Merzba cher disease in 4 patients from 3 Chinese families with Pelizaeus-Merz bacher disease with no detectable exonic mutations, These results supp ort the hypothesis that proteolipid protein gene duplication may be a major cause of Pelizaeus-Merzbacher disease in all ethnic groups and a lso suggest that the molecular diagnosis of Pelizaeus-Merzbacher disea se should therefore include duplication analysis of proteolipid protei n gene. (C) 1997 by Elsevier Science Inc. All rights reserved.