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Review
. 2016;17(10):813-820.
doi: 10.1631/jzus.B1600085.

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

Zhang-Biao Long  1 , Yong-Wei Wang  2   3 , Chen Yang  1 , Gang Liu  3 , Ya-Li Du  1 , Guang-Jun Nie  3 , Yan-Zhong Chang  2 , Bing Han  1
Affiliations
Review

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

Zhang-Biao Long et al. J Zhejiang Univ Sci B. 2016.

Abstract

Erythropoietic protoporphyria (EPP), an autosomal dominant disease, is caused by partial deficiency of ferrochelatase (FECH), which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630-634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene (c.973 delA) in one proband (patient A) and a pathogenic FECH mutation (c.1232 G>T) in the other (patient B) and also observed some nucleotide variations (c.798 C>G, c.921 A>G, IVS1-23 C>T, IVS3+23 A>G, IVS9+35 C>T, and IVS3-48 T>C) in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient's relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.

Keywords: Chinese patients; Clinical manifestation; Erythropoietic protoporphyria; Ferrochelatase; Missense mutations.

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Conflict of interest statement

Compliance with ethics guidelines: Zhang-biao LONG, Yong-wei WANG, Chen YANG, Gang LIU, Ya-li DU, Guang-jun NIE, Yan-zhong CHANG, and Bing HAN declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.

Figures

Fig. 1
Fig. 1
Chronic skin lesions of these two patients (a) Sun-induced skin lesions on the dorsum of the hands of patient A. (b) Scarring and jaundice appearance on the face of patient A. (c) Slight skin change on the dorsum of the hands of patient B due to sun exposure. (d) Sun-induced slight skin change on the face of patient B
Fig. 2
Fig. 2
Plasma fluorescent spectrum assay (a) Plasma fluorescent spectrum assay of the patient A and the emission peak at 632 nm. (b) Plasma fluorescent spectrum assay of the patient B and the emission peak at 630 nm
Fig. 3
Fig. 3
Mapping of the potential pathogenic mutations in the FECH gene in the patient A and patient B and the protein analysis
Fig. 4
Fig. 4
Highly conserved C411F among FECH proteins from several mammalian species The amino acid sequence of the FECH proteins from these mammalian species can get in NCBI database
Fig. 5
Fig. 5
Family pedigree of the patient A based on the nucleotide variations of the patient A and his direct relatives
Fig. 6
Fig. 6
Quantification of the FECH gene region via real-time PCR analysis for the observation of violating the laws of genetics in the family of patient A The result demonstrates no significant difference in FECH copy number among the studied subjects. C1: healthy control 1; C2: healthy control 2; S1: sister 1 of the patient A; S: son of the sister 1 of the patient A
Fig. 7
Fig. 7
Process schematic of EPP diagnosis and management
See this image and copyright information in PMC

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