Molecular epidemiology of erythropoietic protoporphyria in the U.K.

[erythropoietic protoporphyria]

Erythropoietic protoporphyria (EPP ) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH ) or , less frequently , the delta-aminolaevulinate synthase 2 (ALAS 2 ) gene . Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance .To investigate the molecular epidemiology of EPP in the U .K .DNA samples from 191 unrelated patients resident in the U .K . were analysed for mutations in the FECH and ALAS 2 genes and for the FECH IVS 3 -48 dimorphism .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 ALAS 2 mutations (X-linked dominant protoporphyria ). The FECH IVS 3 -48 C allele was strongly associated with psdEPP and with the absence of mutations at the FECH or ALAS 2 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 + 2 T >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 .These data define the prevalence and molecular epidemiology of each type of EPP in the U .K .