Genetic Testing for Hereditary Pancreatitis: Guidelines for Indications, Counselling, Consent and Privacy Issues

Abstract

The identification of point mutations in the cationic trypsinogen (PRSS1) gene that underlie hereditary pancreatitis (HP) has added a valuable diagnostic test to the investigation of acute and chronic pancreatitis. A small blood sample will allow a comparatively cheap test to be performed by paediatricians, gastroenterologists and pancreatic surgeons. Testing DNA for such a high-risk, highpenetrance gene is non-invasive when compared to current investigations, e.g. ERCP or pancreatic function testing. However, the possible adverse effects of unrestrained molecular genetic testing must be emphasized. Mutation testing for the commoner R122H and N29I (and A16V) mutations in the cationic trypsinogen (serine protease, PRSS1) gene (OMIM No. 276000) has previously been performed under the regulation of Ethics Committee Approved Research Protocols. It is now frequently requested in routine clinical practice and as a consequence is becoming more widely available via health service-funded or commercial molecular genetics testing laboratories outside the research setting. In this document, we refer to PRSS1 mutation testing for HP, as this is currently accepted as a clinically useful genetic test, outside the context of a research study. Research programmes are looking at other genes that may be involved in the development of pancreatitis, e.g. PSTI/SPINK1 [Witt et al., 2000; Pfutzer et al., 2000], and the role of mutations in the cystic fibrosis (CFTR) gene [Sharer et al., 1998; Cohn et al., 1998] in determining chronic pancreatitis. More gene(s) and their mutation(s) will be defined for HP, and ultimately for familial pancreatic cancer as research proceeds. We would expect these consensus guidelines to apply to new tests as they are developed and recognized to be clinically useful in the service setting. At present, we only regard PRSS1 mutation testing as of clinical service benefit. All other molecular genetic tests for pancreatitis should currently (July, 2001) be performed on a research basis with an appropriate Research Ethics Committee Approved Protocol. This paper summarizes the current situation and suggests proper ethical principles upon which we believe service-based genetic testing should proceed. We propose consensus guidelines for ethical molecular genetic testing