The hereditary pancreatitis gene maps to long arm of chromosome 7

Bodic, L. Le; Bignon, Jean-Denis; Raguénès, Odile; Mercier, Bernard; Georgelin, T; Schnee, M.; Soulard, F; Gagne, Katia; Bonneville, Françoise; Muller, Jean‐Yves; Bachner, Lucien; Férec, Claude

doi:10.1093/hmg/5.4.549

Cited by 167 publications

(84 citation statements)

References 18 publications

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“…Using a genome-wide genetic linkage analysis, we mapped one HP gene to chromosome 7q35 in a large French HP family in 1996. 11 This linkage was concurrently identified by Whitcomb et al 10 and confirmed by Pandya et al…”

Section: Mapping Of One Hp Gene To Chromosome 7q35 By Genome-wide Linmentioning

confidence: 54%

Molecular basis of hereditary pancreatitis

Chen¹,

Férec²

2000

Eur J Hum Genet

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Hereditary pancreatitis (HP) is an autosomal dominant disease. Two heterozygous missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen gene have been clearly associated with HP. The 'self-destruct' model proposed for the R122H mutation is discussed in connection with the existing theory of pancreatitis, and the basic biochemistry and physiology of trypsinogen, with particular reference to R122 as the primary autolysis site of the cationic trypsinogen. Two different genetic mechanisms are identified which cause the R122H mutation, and gene conversion is the likely cause of the N29I mutation. A unifying model, which highlights an indirect impairment on the R122 autolysis site is hypothesised for the N29I mutation. Possible predisposition to pancreatitis by additional DNA variants in the gene, such as the A16V signal peptide cleavage site mutation and the K23R activation peptide cleavage site mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations detected in HP families are re-evaluated. Finally, large scale association studies are expected to clarify the additional variants' role in pancreatitis and to identify new HP genes.

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Section: Mapping Of One Hp Gene To Chromosome 7q35 By Genome-wide Linmentioning

confidence: 54%

Molecular basis of hereditary pancreatitis

Chen¹,

Férec²

2000

Eur J Hum Genet

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“…After genome-wide linkage analyses, three independent groups reported an association of the hereditary pancreatitis phenotype with the long arm of chromosome 7 [Le Bodic et al, 1996b;Pandya et al, 1996;Whitcomb et al, 1996b]. Within the same year, the c.365G4A mutation (p.R122H; p.R117H in the chymotrypsin numbering system) of the cationic trypsinogen gene was identified in all hereditary pancreatitis-affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals [Whitcomb et al, 1996a].…”

Section: Mutations and Their Biological Relevance The R122h And N29i mentioning

confidence: 99%

Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis

et al. 2006

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“…Mutations in serine protease 1 or cationic trypsinogen (CT, PRSS1) gene have been initially identified as a causative mutation for HP [4,5] . PRSS1 encodes CT protein, which plays a crucial role in food digestion at the duodenum.…”

Section: Introductionmentioning

confidence: 99%

A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation inPRSS1gene

Pho-iam¹

2005

WJG

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AIM:To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer. METHODS: Polymerase chain reaction and directsequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis. Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects. RESULTS:A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C>T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT>TGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects. CONCLUSION:Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.

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The hereditary pancreatitis gene maps to long arm of chromosome 7

Cited by 167 publications

References 18 publications

Molecular basis of hereditary pancreatitis

Molecular basis of hereditary pancreatitis

Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis

A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation inPRSS1gene

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