PMID- 9187667
OWN - NLM
STAT- MEDLINE
DCOM- 19970708
LR  - 20231213
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 99
IP  - 6
DP  - 1997 Jun
TI  - Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish 
      ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with 
      liability to pressure palsies.
PG  - 746-54
AB  - Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to 
      pressure palsies (HNPP) are two inherited peripheral neuropathies. The most 
      prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, 
      respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in 
      the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), 
      myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT 
      patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Dejerine-Sottas 
      neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families 
      lacking a deletion. We have investigated point and small mutations in the MPZ, 
      PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients 
      without duplications, and 5 HNPP patients without deletions. We found 15 
      different mutations in 16 CMT patients (34%). Nine different mutations in ten 
      patients were detected in the Cx32 gene, this being the most frequently involved 
      gene in this series, whereas five mutations involved the MPZ gene and only one 
      the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene 
      involved two codons encoding arginine at positions 164 and 183, suggesting that 
      these two codons may constitute two Cx32 regions prone to mutate in the Spanish 
      population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1 
      of the PMP22 gene in a family with autosomal dominance, which confirms allelic 
      heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this 
      mutation might behave as a null allele.
FAU - Bort, S
AU  - Bort S
AD  - Genetics Unit, Hospital Universitari La Fe, Valencia, Spain.
FAU - Nelis, E
AU  - Nelis E
FAU - Timmerman, V
AU  - Timmerman V
FAU - Sevilla, T
AU  - Sevilla T
FAU - Cruz-Martinez, A
AU  - Cruz-Martinez A
FAU - Martinez, F
AU  - Martinez F
FAU - Millan, J M
AU  - Millan JM
FAU - Arpa, J
AU  - Arpa J
FAU - Vilchez, J J
AU  - Vilchez JJ
FAU - Prieto, F
AU  - Prieto F
FAU - Van Broeckhoven, C
AU  - Van Broeckhoven C
FAU - Palau, F
AU  - Palau F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Connexins)
RN  - 0 (Myelin P0 Protein)
RN  - 0 (Myelin Proteins)
RN  - 0 (PMP22 protein, human)
SB  - IM
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Connexins/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Deletion
MH  - Humans
MH  - Male
MH  - Models, Molecular
MH  - Mutation
MH  - Myelin P0 Protein/*genetics
MH  - Myelin Proteins/*genetics
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Gap Junction beta-1 Protein
EDAT- 1997/06/01 00:00
MHDA- 1997/06/01 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/06/01 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
AID - 10.1007/s004390050442 [doi]
PST - ppublish
SO  - Hum Genet. 1997 Jun;99(6):746-54. doi: 10.1007/s004390050442.