Hereditary pancreatitis caused by triplication of the trypsinogen locus.
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 approximately 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.
Le Maréchal
Cédric
C
Institut National de la Santé et de la Recherche Médicale (INSERM), U613, 29220 Brest, France.
Masson
Emmanuelle
E
Chen
Jian-Min
JM
Morel
Frédéric
F
Ruszniewski
Philippe
P
Levy
Philippe
P
Férec
Claude
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010195:Pancreatitis / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin