Molecular epidemiology of erythropoietic protoporphyria in the U.K

Summary Background  Erythropoietic protoporphyria (EPP) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH) or, less frequently, the delta‐aminolaevulinate synthase 2 (ALAS2) gene. Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of...

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Bibliographic Details
Published in:British journal of dermatology (1951) 2010-03, Vol.162 (3), p.642-646
Main Authors: Whatley, S.D., Mason, N.G., Holme, S.A., Anstey, A.V., Elder, G.H., Badminton, M.N.
Format: Article
Language:English
Subjects:
5-Aminolevulinate Synthetase - genetics
5-Aminolevulinate Synthetase - metabolism
ALAS2
Biological and medical sciences
Cross-Sectional Studies
Dermatology
DNA Mutational Analysis - methods
erythropoietic protoporphyria
ferrochelatase
Ferrochelatase - genetics
Ferrochelatase - metabolism
Genetic Predisposition to Disease - genetics
Humans
Medical sciences
Metabolic diseases
Mutation - genetics
mutations
Other metabolic disorders
Pedigree
Pigments (porphyrias, hyperbilirubinemias...)
Prevalence
Protoporphyria, Erythropoietic - epidemiology
Protoporphyria, Erythropoietic - genetics
Sequence Analysis, DNA
Skin involvement in other diseases. Miscellaneous. General aspects
Statistics as Topic
United Kingdom - epidemiology
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Summary:Summary Background  Erythropoietic protoporphyria (EPP) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH) or, less frequently, the delta‐aminolaevulinate synthase 2 (ALAS2) gene. Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance. Objectives  To investigate the molecular epidemiology of EPP in the U.K. Methods  DNA samples from 191 unrelated patients resident in the U.K. were analysed for mutations in the FECH and ALAS2 genes and for the FECH IVS3‐48 dimorphism. Results  Mutations were identified in 179 (94%) patients. Most (169; 94%) had a FECH mutation on one allele and were classified as having pseudodominant EPP (psdEPP); seven (4%) patients had FECH mutations on both alleles (autosomal recessive EPP) and three (2%) patients had ALAS2 mutations (X‐linked dominant protoporphyria). The FECH IVS3‐48C allele was strongly associated with psdEPP and with the absence of mutations at the FECH or ALAS2 loci. Fifty‐six FECH mutations were identified, 19 being previously unreported. Missense mutations were predominant in autosomal recessive EPP (82%) but not in psdEPP (32%). One mutation (c.314 + 2T>G) was present in 41 (24%) of EPP families, most of whom appeared to be descended from a common ancestor resident in the north of England. Conclusions  These data define the prevalence and molecular epidemiology of each type of EPP in the U.K.
ISSN:0007-0963
1365-2133
DOI:10.1111/j.1365-2133.2010.09631.x