Predictive diagnosis of multiple endocrine neoplasia (MEN 1) in four Australian kindreds

Background: Multiple endocrine neoplasia type 1 (MEN 1) is a tumour predisposition syndrome that usually manifests in the first four decades of life. It has an autosomal dominant mode of inheritance which means that any new member of a MEN1 kindred has roughly a 50% chance of developing the disorder during their lifetime. The localisation of the MEN1 gene to a small region of chromosome band llql3 has led to the development of DNA-based predictive diagnosis for this disease. Aims: To establish a polymerase chain reaction (PCR)-based system, using simple tandem repeat polymorphisms (STRPs), to predict gene carriers in four Australian MEN 1 kindreds. Funding: This work was supported by the National Health and Medical Research Council of Australia and the Princess Alexandra Hospital Foundation. Methods: Six STRP markers flanking the MEN1 region of chromosome band 11q13 were used to screen individuals for a common haplotype in order to determine carrier status. Results: The accuracy of prediction was calculated to be >95% in informative individuals. Conclusions: DNA-based presymptomatic detection of affected members of MEN 1 kindreds could facilitate their care and reduce the inconvenience and expense of repeated testing of unaffected members. However, due to occasional recombination events or uninformativeness of markers in certain individuals, carrier status cannot always be predicted.