title: Heterogeneity in hereditary pancreatitis.
abstract: Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for approximately 25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic "at-risk" relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232, USA. majed.dasouki@mcmail.vanderbilt.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Dasouki
authors.forename: J
authors.initials: J
authors.lastname: Cogan
authors.forename: M L
authors.initials: ML
authors.lastname: Summar
authors.forename: W
authors.initials: W
authors.lastname: Neblitt
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: D
authors.initials: D
authors.lastname: Koller
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D008297:Male; D010195:Pancreatitis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014362:Trypsinogen / Q000235:genetics
chemical_list: D005819:Genetic Markers; D014362:Trypsinogen