A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR.
Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10%-25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be a important genetic abnormality in PMD and affect myelin formation.
Inoue
K
K
Department of Psychiatry, Yokohama City University, School of Medicine, Yokohama.
Osaka
H
H
Sugiyama
N
N
Kawanishi
C
C
Onishi
H
H
Nezu
A
A
Kimura
K
K
Yamada
Y
Y
Kosaka
K
K
D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D009185:Myelin Proteins / Q000235:genetics; D010290:Parents; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C078341:MYT1 protein, human; D009185:Myelin Proteins; C073687:PMP22 protein, human; D014157:Transcription Factors; D004247:DNA