Hereditary pancreatitis caused by triplication of the trypsinogen locus

被引：151

作者：

Le Marechal, Cedric

Masson, Emmanuelle

Chen, Jian-Min ^{[1
]}

Morel, Frederic

Ruszniewski, Philippe

Levy, Philippe

Ferec, Claude

机构：

[1] INSERM, U613, F-29220 Brest, France

[2] Univ Bretagne Occidentale, Fac Med Brest & Sci Sante, F-29238 Brest, France

[3] CHU Brest, Hop Morvan, Lab Genet Mol & Histocompatibil, F-29220 Brest, France

[4] Etablissement Francais Sang Bretagne, F-29220 Brest, France

[5] CHRU Brest, Hop Morvan, Serv Cytogenet Cytol & Biol Reprod, F-29238 Brest, France

[6] Hop Beaujon, AP HP, Pole Maladies Appareil Digest, F-92118 Clichy, France

来源：

NATURE GENETICS | 2006年 / 38卷 / 12期

关键词：

D O I：

10.1038/ng1904

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hereditary pancreatitis has been reported to be caused by 'gain-of-function' missense mutations in the cationic trypsinogen gene (PRSS1). Here we report the triplication of a similar to 605-kb segment containing the PRSS1 gene on chromosome 7 in five families with hereditary pancreatitis. This triplication, which seems to result in a gain of trypsin through a gene dosage effect, represents a previously unknown molecular mechanism causing hereditary pancreatitis.

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页码：1372 / 1374

页数：3

相关论文

共 15 条

[1] Genomic rearrangements in the CFTR gene:: Extensive allelic heterogeneity and diverse mutational mechanisms [J].

Audrézet, M ;

Chen, JM ;

Raguénès, O ;

Chuzhanova, N ;

Giteau, K ;

Le Maréchal, C ;

Quéré, I ;

Cooper, DN ;

Férec, C .

HUMAN MUTATION, 2004, 23 (04) :343-357

[2] Loss of function mutations in the cationic trypsinogen gene (PRSS1) may act as a protective factor against pancreatitis [J].

Chen, JM ;

Le Maréchal, C ;

Lucas, D ;

Raguénès, O ;

Férec, C .

MOLECULAR GENETICS AND METABOLISM, 2003, 79 (01) :67-70

[3]

CHIARA H, 1896, Z HEILKUNDE, V17, P70

[4]

COMFORT MW, 1952, GASTROENTEROLOGY, V21, P54

[5] PROTEOLIPID PROTEIN GENE DOSAGE EFFECT IN PELIZAEUS-MERZBACHER DISEASE [J].

ELLIS, D ;

MALCOLM, S .

NATURE GENETICS, 1994, 6 (04) :333-334

[6] The hereditary pancreatitis gene maps to long arm of chromosome 7 [J].

LeBodic, L ;

Bignon, JD ;

Raguenes, O ;

Mercier, B ;

Georgelin, T ;

Schnee, M ;

Soulard, F ;

Gagne, K ;

Bonneville, F ;

Muller, JY ;

Bachner, L ;

Ferec, C .

HUMAN MOLECULAR GENETICS, 1996, 5 (04) :549-554

[7] DNA DUPLICATION ASSOCIATED WITH CHARCOT-MARIE-TOOTH DISEASE TYPE-1A [J].

LUPSKI, JR ;

DEOCALUNA, RM ;

SLAUGENHAUPT, S ;

PENTAO, L ;

GUZZETTA, V ;

TRASK, BJ ;

SAUCEDOCARDENAS, O ;

BARKER, DF ;

KILLIAN, JM ;

GARCIA, CA ;

CHAKRAVARTI, A ;

PATEL, PI .

CELL, 1991, 66 (02) :219-232

[8] APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy [J].

Rovelet-Lecrux, A ;

Hannequin, D ;

Raux, G ;

Le Meur, N ;

Laquerrière, A ;

Vital, A ;

Dumanchin, C ;

Feuillette, S ;

Brice, A ;

Vercelletto, M ;

Dubas, F ;

Frebourg, T ;

Campion, D .

NATURE GENETICS, 2006, 38 (01) :24-26

[9] The complete 685-kilobase DNA sequence of the human beta T cell receptor locus [J].

Rowen, L ;

Koop, BF ;

Hood, L .

SCIENCE, 1996, 272 (5269) :1755-1762

[10] Biochemical models of hereditary pancreatitis [J].

Sahin-Toth, Miklos .

ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA, 2006, 35 (02) :303-+