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.
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.
Authors: Manisha Balwani; Hetanshi Naik; Karl E Anderson; D Montgomery Bissell; Joseph Bloomer; Herbert L Bonkovsky; John D Phillips; Jessica R Overbey; Bruce Wang; Ashwani K Singal; Lawrence U Liu; Robert J Desnick Journal: JAMA Dermatol Date: 2017-08-01 Impact factor: 10.282
Authors: Eric W Gou; Manisha Balwani; D Montgomery Bissell; Joseph R Bloomer; Herbert L Bonkovsky; Robert J Desnick; Hetanshi Naik; John D Phillips; Ashwani K Singal; Bruce Wang; Sioban Keel; Karl E Anderson Journal: Clin Chem Date: 2015-10-19 Impact factor: 8.327
Authors: Manisha Balwani; Dana Doheny; David F Bishop; Irina Nazarenko; Makiko Yasuda; Harry A Dailey; Karl E Anderson; D Montgomery Bissell; Joseph Bloomer; Herbert L Bonkovsky; John D Phillips; Lawrence Liu; Robert J Desnick Journal: Mol Med Date: 2013-04-30 Impact factor: 6.354