Objective: The R122H mutation represents the most common point mutation of the cationic trypsinogen gene (PRSS1) in patients with hereditary pancreatitis (HP; Online Mendelian inheritance in man [OMIM] 167800), a rare variety of chronic pancreatitis. We identified a large number of HP families carrying this mutation in a confined region of Northern Germany within a 100-km radius. This apparent clustering could be due to the inheritance from a common ancestor (founder effect).
Methods: To address this question, we genotyped SNPs in close vicinity of the PRSS1 locus and determined common haplotypes.
Results: In members from 10 unrelated HP families (all R122H-positive), we found 7 different haplotypes to segregate with the R122H mutation.
Conclusions: This virtually excludes a founder effect and suggests the presence of a mutational hot spot in codon 122 of the PRSS1 gene. An ascertainment bias of a large-volume referral center may have contributed to the locally increased detection of HP cases.