PMID- 10417279
OWN - NLM
STAT- MEDLINE
DCOM- 19990820
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 2
DP  - 1999 Aug
TI  - Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher
      Disease: duplications, the major cause of the disease, originate more frequently 
      in male germ cells, but point mutations do not. The Clinical European Network on 
      Brain Dysmyelinating Disease.
PG  - 360-9
AB  - Pelizaeus-Merzbacher Disease (PMD) is an X-linked developmental defect of
      myelination affecting the central nervous system and segregating with the
      proteolipoprotein (PLP) locus. Investigating 82 strictly selected sporadic cases 
      of PMD, we found PLP mutations in 77%; complete PLP-gene duplications were the
      most frequent abnormality (62%), whereas point mutations in coding or splice-site
      regions of the gene were involved less frequently (38%). We analyzed the maternal
      status of 56 cases to determine the origin of both types of PLP mutation, since
      this is relevant to genetic counseling. In the 22 point mutations, 68% of mothers
      were heterozygous for the mutation, a value identical to the two-thirds of
      carrier mothers that would be expected if there were an equal mutation rate in
      male and female germ cells. In sharp contrast, among the 34 duplicated cases, 91%
      of mothers were carriers, a value significantly (chi2=9. 20, P<.01) in favor of a
      male bias, with an estimation of the male/female mutation frequency (k) of 9.3.
      Moreover, we observed the occurrence of de novo mutations between parental and
      grandparental generations in 17 three-generation families, which allowed a direct
      estimation of the k value (k=11). Again, a significant male mutation imbalance
      was observed only for the duplications. The mechanism responsible for this strong
      male bias in the duplications may involve an unequal sister chromatid exchange,
      since two deletion events, responsible for mild clinical manifestations, have
      been reported in PLP-related diseases.
FAU - Mimault, C
AU  - Mimault C
AD  - INSERM U.384-Faculte de Medecine, Clermont-Ferrand Cedex, France.
FAU - Giraud, G
AU  - Giraud G
FAU - Courtois, V
AU  - Courtois V
FAU - Cailloux, F
AU  - Cailloux F
FAU - Boire, J Y
AU  - Boire JY
FAU - Dastugue, B
AU  - Dastugue B
FAU - Boespflug-Tanguy, O
AU  - Boespflug-Tanguy O
LA  - eng
SI  - OMIM/132080
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (CFTR protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MYT1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/genetics
MH  - DNA Mutational Analysis
MH  - DNA-Binding Proteins/*genetics
MH  - Diffuse Cerebral Sclerosis of Schilder/*genetics
MH  - Family Health
MH  - Female
MH  - Gene Dosage
MH  - *Gene Duplication
MH  - Gene Frequency
MH  - Germ Cells/*metabolism
MH  - Haplotypes
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Mothers
MH  - Point Mutation/*genetics
MH  - Polymerase Chain Reaction/methods
MH  - Polymorphism, Genetic/genetics
MH  - Reproducibility of Results
MH  - Sex Characteristics
MH  - Transcription Factors/*genetics
PMC - PMC1377935
EDAT- 1999/07/27 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/07/27 10:00
PHST- 1999/07/27 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/07/27 10:00 [entrez]
AID - S0002-9297(07)62053-9 [pii]
AID - 10.1086/302483 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Aug;65(2):360-9. doi: 10.1086/302483.