Premium
A homoallelic FECH mutation in a patient with both erythropoietic protoporphyria and palmar keratoderma
Author(s) -
Minder EI,
SchneiderYin X,
Mamet R,
Horev L,
Neuenschwander S,
Baumer A,
Austerlitz F,
Puy H,
Schoenfeld N
Publication year - 2010
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/j.1468-3083.2010.03640.x
Subject(s) - genetics , erythropoietic protoporphyria , haplotype , missense mutation , medicine , penetrance , consanguinity , mutation , disease gene identification , microsatellite , palmoplantar keratoderma , allele , biology , hyperkeratosis , gene , exome sequencing , protoporphyrin , phenotype , biochemistry , porphyrin
Background Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by the deficiency of ferrochelatase (FECH) in the haem biosynthetic pathway. In the majority of families, EPP is transmitted as a pseudodominant trait. Autosomal recessive form of EPP is found in only about 3% of the families. Objectives In this study, we describe a 6‐year‐old boy who suffered from both EPP and palmar keratoderma. Methods and Results A novel homoallelic missense mutation (p.Ser318Tyr) was identified in the FECH gene. In addition, a region of homozygosity of approximately 6.8 Mb was observed in chromosome 18 of the patient by both microsatellite and SNP array. The parents of the patient, both of Palestinian (Jordanian) origin, were heterozygous for the S318Y mutation, although no history of consanguinity was known. Microsatellite genotyping identified a partial haplotype from each parent that corresponds to the region of homozygosity in the patient. Assuming S318Y is a founder mutation, the number of generations separating the two parents from their common ancestor from whom they inherited S318Y was estimated as 21.7 (95% CI 3.42–69.7). Conclusion EPP was therefore inherited as an autosomal recessive trait in the family. This study confirms the association between palmar keratoderma and autosomal recessive EPP.