A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene.
OBJECTIVE
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 direct sequencing 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.


CONCLUSIONS
Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.
Pho-Iam
Theeraphong
T
Division of Medical Genetics, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Thongnoppakhun
Wanna
W
Yenchitsomanus
Pa-Thai
PT
Limwongse
Chanin
C
D005091:Exons; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D010195:Pancreatitis / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology; D014357:Trypsin / Q000235:genetics*; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin