Finding the genetic mutation for hereditary pancreatitis (HP) on chromosome 7q35 (Whitcomb et al. 1996) may suggest a new genetic screening for this disease. We previously identified three families from WV (Elitsur et al. 1994).

Aims: To detect HP mutation by linkage analysis to genetic markers on 7q and to investigate the diagnostic value of this mutation in the HP gene for patients with HP.

Methods: Sixty four members of three families clinically diagnosed with HP, or with a reliable positive medical history for HP were recruited. The genomic DNA was extracted from patients PBLs. The LINKAGE program was used to calculate the LOD score between markers on the HP gene. The A to G mutation was detected by amplification (PCR) and digestion by the restriction enzyme Afl III.

Results: Linkage analysis showed a combined LOD score of 4.34, 3.59, 4.49, 2.91, 3.24, and 1.94 for STR markers D7S661*, D7S2511*, D7S1805*, D7S1826, D7S2208*, and D7S798, respectively. Linkage to four out of six markers was significant (* LOD>3.0). The G to A mutation was present in 28/64 members. All of 26 clinically affected members, and 2 out of 25 clinically unaffected members (obligate carriers), carried the mutation. None of the 13 married-in members carried the mutation. Restriction analysis test showed a sensitivity, specificity, positive and negative predictive values of 1.0, 0.92, 0.92, and 1.0, respectively.

Conclusion: (1) HP mutation is linked to genetic markers on the long arm of chromosome 7. (2) Detecting the G to A mutation may be a useful tool for screening individuals from families with HP.