Heterogeneity in hereditary pancreatitis

✍ Scribed by Dasouki, Majed J.; Cogan, Joy; Summar, Marshall L.; Neblitt, Wallace; Foroud, Tatiana; Koller, Dan; Phillips, John A.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 41 KB
• Volume: 77
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19980428)77:1<47::aid-ajmg11>3.0.co;2-o

✦ Synopsis

Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ∼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. Am.