GENETICS OF PELIZAEUS-MERZBACHER DISEASE

Pelizaeus-Merzbacher disease (PMD) has been recognized as a clinical e ntity for more than a century. It has gradually become apparent that t he disorder is a dysmyelination, in distinction to demyelinating condi tions such as adrenoleukodystrophy. The failure to deposit myelin is d ue to decreased production of its chief protein, proteolipid protein ( PLP). In about 30% of patients with the diagnosis of PMD there is a mu tation in the coding portion of the proteolipid protein gene, PLP. Thi s gene is located at Xq22 so the disease in these families shows an X- linked pattern of inheritance. The expression of the mutant gene is ge nerally recessive, but some mutations are expressed frequently in fema les. At least some patients with PMD that do not show mutations in the coding region of PLP demonstrate linkage between the disease and PLP. As additional mutations in PLP are discovered, it is becoming apparen t that the nosology of PLP-associated disease is changing. PMD now com prises a spectrum of disorders with similar but not necessarily identi cal clinical pictures. Some of these disorders may be certain forms of X-linked paraplegia, SPG2. Finally, some diseases that look like PMD may not be X-linked.