PMID- 10486317
OWN - NLM
STAT- MEDLINE
DCOM- 20001002
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 4
DP  - 1999 Oct
TI  - Variegate porphyria in Western Europe: identification of PPOX gene mutations in
      104 families, extent of allelic heterogeneity, and absence of correlation between
      phenotype and type of mutation.
PG  - 984-94
AB  - Variegate porphyria (VP) is a low-penetrance, autosomal dominant disorder
      characterized clinically by skin lesions and acute neurovisceral attacks that
      occur separately or together. It results from partial deficiency of
      protoporphyrinogen oxidase encoded by the PPOX gene. VP is relatively common in
      South Africa, where most patients have inherited the same mutation in the PPOX
      gene from a common ancestor, but few families from elsewhere have been studied.
      Here we describe the molecular basis and clinical features of 108 unrelated
      patients from France and the United Kingdom. Mutations in the PPOX gene were
      identified by a combination of screening (denaturing gradient gel
      electrophoresis, heteroduplex analysis, or denaturing high-performance liquid
      chromatography) and direct automated sequencing of amplified genomic DNA. A total
      of 60 novel and 6 previously reported mutations (25 missense, 24 frameshift, 10
      splice site, and 7 nonsense) were identified in 104 (96%) of these unrelated
      patients, together with 3 previously unrecognized single-nucleotide
      polymorphisms. VP is less heterogeneous than other acute porphyrias; 5 mutations 
      were present in 28 (26%) of the families, whereas 47 mutations were restricted to
      1 family; only 2 mutations were found in both countries. The pattern of clinical 
      presentation was identical to that reported from South Africa and was not
      influenced by type of mutation. Our results define the molecular genetics of VP
      in western Europe, demonstrate its allelic heterogeneity outside South Africa,
      and show that genotype is not a significant determinant of mode of presentation.
FAU - Whatley, S D
AU  - Whatley SD
AD  - Department of Medical Biochemistry, University of Wales College of Medicine,
      Heath Park, Cardiff, UK.
FAU - Puy, H
AU  - Puy H
FAU - Morgan, R R
AU  - Morgan RR
FAU - Robreau, A M
AU  - Robreau AM
FAU - Roberts, A G
AU  - Roberts AG
FAU - Nordmann, Y
AU  - Nordmann Y
FAU - Elder, G H
AU  - Elder GH
FAU - Deybach, J C
AU  - Deybach JC
LA  - eng
SI  - GENBANK/AL021186
SI  - GENBANK/D83139
SI  - GENBANK/D85417
SI  - GENBANK/M73709
SI  - GENBANK/M97208
SI  - GENBANK/U18778
SI  - GENBANK/U25114
SI  - GENBANK/X99450
SI  - GENBANK/Y13466
SI  - GENBANK/Y13467
SI  - OMIM/176200
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 (Flavoproteins)
RN  - 0 (Mitochondrial Proteins)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors)
RN  - EC 1.3.3.4 (PPOX protein, human)
RN  - EC 1.3.3.4 (Protoporphyrinogen Oxidase)
SB  - IM
MH  - *Alleles
MH  - Amino Acid Sequence
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Female
MH  - Flavoproteins
MH  - France
MH  - Gene Frequency/genetics
MH  - *Genetic Heterogeneity
MH  - Genetic Testing
MH  - Genotype
MH  - Humans
MH  - Introns/genetics
MH  - Male
MH  - Mitochondrial Proteins
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Oxidoreductases/chemistry/*genetics
MH  - *Oxidoreductases Acting on CH-CH Group Donors
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Porphyrias, Hepatic/*enzymology/*genetics/physiopathology
MH  - Protoporphyrinogen Oxidase
MH  - South Africa
MH  - United Kingdom
PMC - PMC1288269
EDAT- 1999/09/16 09:00
MHDA- 2000/10/07 11:01
CRDT- 1999/09/16 09:00
PHST- 1999/09/16 09:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 1999/09/16 09:00 [entrez]
AID - S0002-9297(07)62601-9 [pii]
AID - 10.1086/302586 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Oct;65(4):984-94. doi: 10.1086/302586.