A missense mutation in the proteolipid protein gene responsible for Pelizaeus—Merzbacher disease in a Japanese family

We investigated the proteolipid protein (PLP) gene of two boys in a Japanese family with Pelizaeus—Merzbacher disease (PMD), an X-linked neurologic disorder characterized by dysmyelination in the central nervous system (CNS). The patients showed similar clinical signs from birth and autopsy on the e...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 1993-01, Vol.2 (1), p.19-22
Main Authors: Iwaki, Akiko, Muramoto, Tamaki, Iwaki, Toru, Furumi, Hiroyasu, Dario-deLeon, Maria L., Tateishi, Jun, Fukumaki, Yasuyuki
Format: Article
Language:English
Subjects:
Adolescent
Alleles
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Brain - metabolism
Brain - pathology
Child
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Diffuse Cerebral Sclerosis of Schilder - genetics
Diffuse Cerebral Sclerosis of Schilder - pathology
Female
genes
Humans
Japan
Male
man
Medical sciences
missense mutant
Molecular Sequence Data
Myelin Proteins - genetics
Myelin Proteolipid Protein
Neurology
Oligodendroglia - pathology
Oligodeoxyribonucleotides
Pelizaeus-Merzbacher disease
Polymerase Chain Reaction
proteolipid protein
RNA, Messenger - genetics
RNA, Messenger - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We investigated the proteolipid protein (PLP) gene of two boys in a Japanese family with Pelizaeus—Merzbacher disease (PMD), an X-linked neurologic disorder characterized by dysmyelination in the central nervous system (CNS). The patients showed similar clinical signs from birth and autopsy on the elder brother confirmed a connatal type of PMD. Direct sequencing of the PLP gene and PLP mRNAs from the brain of the PMD patient revealed a G to T transition in exon V of the PLP gene, which leads to a glycine to cystein substitution at residue 220. Allele-specific oligonucleotide hybridization revealed that this mutation was also present in his brother, but was absent in 100 X chromosomes of normal Japanese individuals. Northern blot analysis showed that the mRNA levels of PLP and myelin basic protein, two major myelin proteins produced by oligodendrocytes, were much reduced in the PMD brain, hence, there was a specific loss of oligodendrocytes. It seems likely that the substitution is responsible for PMD (connatal type) in this particular family and causes oligodendrocytes death in the CNS.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/2.1.19