Local clustering of PRSS1 R122H mutations in hereditary pancreatitis patients from Northern Germany.
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.
Weiss
Frank Ulrich
FU
Department of Internal Medicine A, Ernst-Moritz-Arndt-University Greifswald, Germany.
Zenker
Martin
M
Ekici
Arif Bülent
AB
Simon
Peter
P
Mayerle
Julia
J
Lerch
Markus M
MM
D002760:Cholangiopancreatography, Endoscopic Retrograde; D016000:Cluster Analysis; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D050500:Pancreatitis, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; D004247:DNA; C489303:PRSS1 protein, human; D014357:Trypsin