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A homoallelic FECH mutation in a patient with both erythropoietic protoporphyria and palmar keratoderma


Minder, E I; Schneider-Yin, X; Mamet, R; Horev, L; Neuenschwander, S; Baumer, A; Austerlitz, F; Puy, H; Schoenfeld, N (2010). A homoallelic FECH mutation in a patient with both erythropoietic protoporphyria and palmar keratoderma. Journal of the European Academy of Dermatology and Venereology, 24(11):1349-1353.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
04 Faculty of Medicine > Functional Genomics Center Zurich
08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:28 Sep 2010 13:02
Last Modified:05 Apr 2016 14:14
Publisher:Wiley-Blackwell
ISSN:0926-9959
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1111/j.1468-3083.2010.03640.x
PubMed ID:20337824
Permanent URL: http://doi.org/10.5167/uzh-35667

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