PELIZAEUS-MERZBACHER DISEASE CAUSED BY A DE-NOVO MUTATION THAT ORIGINATED IN EXON-2 OF THE MATERNAL GREAT-GRANDFATHER OF THE PROPOSITUS

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disor der of the central nervous system. Many cases of PMD can be attributed to defects in the proteolipid protein gene (PLP). To date, with one e xception, each family has had either no or a unique mutation in one of the seven exons of PLP. We describe a new missense mutation in exon 2 of the PLP gene of an affected individual. This mutation codes for Re instead of Thr at codon 42. The point mutation originated in the X ch romosome of the maternal great-grandfather of the propositus. This was determined from the pattern of inheritance of the AhaII polymorphism and a series of microsatellite markers that are localized near PLP at Xq22. (C) 1995 Wiley-Liss, Inc.