Local clustering of PRSS1 R122H mutations in hereditary pancreatitis patients from Northern Germany.

Abstract

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). To address this question, we genotyped SNPs in close vicinity of the PRSS1 locus and determined common haplotypes. In members from 10 unrelated HP families (all R122H-positive), we found 7 different haplotypes to segregate with the R122H mutation. 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.