A novel large deletion and three polymorphisms in the FECH gene associated with erythropoietic protoporphyria.
BACKGROUND
Erythropoietic protoporphyria (EPP) is known to be inherited in both autosomal dominant and recessive manners. A deleterious mutation in conjunction with a polymorphic wild type allele underlies the molecular basis of the dominant type.


METHODS
We report a patient with EPP who was found to have a novel large deletion [c.1-9628_67+2871del12566 bp] and three polymorphisms [c.1-251A>G, c.68-23C>T and c.315-48T>C] in trans to the deletion in his ferrochelatase (FECH) gene.


RESULTS
The combination of the deletion and the polymorphisms reduced his FECH activity level to 20% of control.


CONCLUSIONS
It is conceivable that a homozygous state for this polymorphic haplotype might be sufficient to produce clinical phenotype of EPP. The boundary between autosomal dominant and autosomal recessive inheritance may not always be distinct.
Li
Chumei
C
Clinical Genetics Program, Department of Pediatrics, McMaster University, Ontario, Canada. lichum@mcmaster.ca
Di Pierro
Elena
E
Brancaleoni
Valentina
V
Cappellini
Maria Domenica
MD
Steensma
David P
DP
D000328:Adult; D005294:Ferrochelatase / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D046351:Protoporphyria, Erythropoietic / Q000235:genetics*; D017384:Sequence Deletion
D005294:Ferrochelatase