PMID- 10406984
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20190501
IS  - 0022-3050 (Print)
IS  - 0022-3050 (Linking)
VI  - 67
IP  - 2
DP  - 1999 Aug
TI  - Novel mutation in the myelin protein zero gene in a family with intermediate
      hereditary motor and sensory neuropathy.
PG  - 174-9
AB  - OBJECTIVES: To determine the molecular basis for autosomal dominant intermediate 
      hereditary motor and sensory neuropathy (HMSN) in a four generation family. The
      gene defects in families with intermediate HMSN are not known, but it has been
      suggested that most have X linked HMSN. METHODS: All participating family members
      were examined clinically. Genomic DNA was obtained from 10 affected and seven
      unaffected members. Linkage analysis for the known HMSN loci was first performed.
      Mutations in the peripheral myelin protein zero gene (PMP0) were sought in two
      affected members, using one unaffected member for comparison, by amplification of
      the six exons of the gene followed by single strand conformation polymorphism
      (SSCP) analysis, dideoxy fingerprinting (ddF), and sequencing. Subsequently, the 
      mutation was screened for in all affected and unaffected members in the family
      using Alu I digestion and in 100 unrelated control subjects using "snap back"
      SSCP analysis. Sequencing of cDNA from a sural nerve biopsy from an affected
      member was also performed. RESULTS: The clinical phenotype was of variable
      severity, with motor nerve conduction velocities in the intermediate range.
      Linkage to PMP0 was demonstrated. Analysis of genomic DNA and cDNA for PMP0
      identified a novel codon 35 GAC to TAC mutation. The mutation produces an
      inferred amino acid change of aspartate to tyrosine at codon six of the processed
      protein (Asp6Tyr) in the extracellular domain and was present in all affected
      family members but not in 100 unrelated controls. CONCLUSIONS: The present
      findings further extend the range of phenotypes associated with PMP0 mutations
      and indicate that families with "intermediate" HMSN need not necessarily be
      X-linked as previously suggested.
FAU - Mastaglia, F L
AU  - Mastaglia FL
AD  - Australian Neuromuscular Research Institute, Departments of Medicine , University
      of Western Australia, Department of Medicine, 6009, Australia.
      flmast@cyllene.uwa.edu.au
FAU - Nowak, K J
AU  - Nowak KJ
FAU - Stell, R
AU  - Stell R
FAU - Phillips, B A
AU  - Phillips BA
FAU - Edmondston, J E
AU  - Edmondston JE
FAU - Dorosz, S M
AU  - Dorosz SM
FAU - Wilton, S D
AU  - Wilton SD
FAU - Hallmayer, J
AU  - Hallmayer J
FAU - Kakulas, B A
AU  - Kakulas BA
FAU - Laing, N G
AU  - Laing NG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (DNA, Complementary)
RN  - 0 (Myelin P0 Protein)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Base Sequence/genetics
MH  - Biopsy
MH  - DNA/genetics
MH  - DNA, Complementary/genetics
MH  - Female
MH  - Genetic Linkage/genetics
MH  - Genome
MH  - Hereditary Sensory and Motor Neuropathy/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation/*physiology
MH  - Myelin P0 Protein/*genetics
MH  - Pedigree
MH  - Sural Nerve/pathology
PMC - PMC1736462
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
AID - 10.1136/jnnp.67.2.174 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):174-9. doi: 10.1136/jnnp.67.2.174.