Title: Evidence in the UK Biobank for the underdiagnosis of erythropoietic protoporphyria.
Authors: Dickey, Amy K; Quick, Corbin; Ducamp, Sarah; Zhu, Zhaozhong; Feng, Yen-Chen A; Naik, Hetanshi; Balwani, Manisha; Anderson, Karl E; Lin, Xihong; Phillips, John E; Rebeiz, Lina; Bonkovsky, Herbert L; McGuire, Brendan M; Wang, Bruce; Chasman, Daniel I; Smoller, Jordan W; Fleming, Mark D; Christiani, David C
Published In Genet Med, (2021 Jan)
Abstract: PURPOSE: Erythropoietic protoporphyria (EPP), characterized by painful cutaneous photosensitivity, results from pathogenic variants in ferrochelatase (FECH). For 96% of patients, EPP results from coinheriting a rare pathogenic variant in trans of a common hypomorphic variant c.315-48T>C (minor allele frequency 0.05). The estimated prevalence of EPP derived from the number of diagnosed individuals in Europe is 0.00092%, but this may be conservative due to underdiagnosis. No study has estimated EPP prevalence using large genetic data sets. METHODS: Disease-associated FECH variants were identified in the UK Biobank, a data set of 500,953 individuals including 49,960 exome sequences. EPP prevalence was then estimated. The association of FECH variants with EPP-related traits was assessed. RESULTS: Analysis of pathogenic FECH variants in the UK Biobank provides evidence that EPP prevalence is 0.0059% (95% confidence interval [CI]: 0.0042-0.0076%), 1.7-3.0 times more common than previously thought in the UK. In homozygotes for the common c.315-48T>C FECH variant, there was a novel decrement in both erythrocyte mean corpuscular volume (MCV) and hemoglobin. CONCLUSION: The prevalence of EPP has been underestimated secondary to underdiagnosis. The common c.315-48T>C allele is associated with both MCV and hemoglobin, an association that could be important both for those with and without EPP.
PubMed ID: 32873934
MeSH Terms: No MeSH terms associated with this publication