The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH

被引：186

作者：

Gouya, L ^{[1
]}

Puy, H ^{[1
]}

Robreau, AM ^{[1
]}

Bourgeois, M ^{[1
]}

Lamoril, J ^{[1
]}

Da Silva, V ^{[1
]}

Grandchamp, B ^{[1
]}

Deybach, JC ^{[1
]}

机构：

[1] Hop Louis Mourier, Fac Xavier Bichat, INSERM, U 409, F-92701 Colombes, France

来源：

NATURE GENETICS | 2002年 / 30卷 / 01期

关键词：

D O I：

10.1038/ng809

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC 4.99.1.1)(1,2). EPP is transmitted as an autosomal dominant disorder(3) with an incomplete penetrance(1). Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3-48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression.

引用

页码：27 / 28

页数：2

共 10 条

[1]

Anderson K.E., 2001, The Metabolib and Molecular Bases of Inherited Disease, P2961

[2] Specific polymorphisms in the RET proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression [J].

Borrego, S ;

Sáez, ME ;

Ruiz, A ;

Gimm, O ;

López-Alonso, M ;

Antiñolo, G ;

Eng, C .

JOURNAL OF MEDICAL GENETICS, 1999, 36 (10) :771-774

[3] RET genotypes comprising specific haplotypes of polymorphic variants predispose to isolated Hirschsprung disease [J].

Borrego, S ;

Ruiz, A ;

Saez, ME ;

Gimm, O ;

Gao, X ;

López-Alonso, M ;

Hernández, A ;

Wright, FA ;

Antiñolo, G ;

Eng, C .

JOURNAL OF MEDICAL GENETICS, 2000, 37 (08) :572-578

[4]

Gouya L, 1996, AM J HUM GENET, V58, P292

[5] Inheritance in erythropoietic protoporphyria: A common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation [J].

Gouya, L ;

Puy, H ;

Lamoril, J ;

Da Silva, V ;

Grandchamp, B ;

Nordmann, Y ;

Deybach, JC .

BLOOD, 1999, 93 (06) :2105-2110

[6] HUMAN ERYTHROPOIETIC PROTOPORPHYRIA - 2-POINT MUTATIONS IN THE FERROCHELATASE GENE [J].

LAMORIL, J ;

BOULECHFAR, S ;

DEVERNEUIL, H ;

GRANDCHAMP, B ;

NORDMANN, Y ;

DEYBACH, JC .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 181 (02) :594-599

[7]

Li F M, 1987, Biomed Chromatogr, V2, P164, DOI 10.1002/bmc.1130020408

[8]

SARKANY RP, 1994, LANCET, V8910, P1394

[9] ERYTHROPOIETIC PROTOPORPHYRIA [J].

TODD, DJ .

BRITISH JOURNAL OF DERMATOLOGY, 1994, 131 (06) :751-766

[10] GENETIC-ASPECTS OF ERYTHROPOIETIC PROTOPORPHYRIA [J].

WENT, LN ;

KLASEN, EC .

ANNALS OF HUMAN GENETICS, 1984, 48 (MAY) :105-117

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