Boman H1,2, Aarsand AK2, Sandberg S2

1Section of Medical Genetics and Molecular Medicine, Institute for Clinical Medicine, University of Bergen, and 2The Norwegian Porphyria Centre (NAPOS), Haukeland University Hospital, N-5021, Bergen, Norway.

The South African PPOX mutation R59W and the HMBS W198X found in the northern parts of Sweden and Norway, are archetypes of founder mutations. In contrast, although the UROD mutation IVS6+1G>C is demonstrated in most published series of PCT patients, UROD mutations are mostly private.

In a Norwegian series of PCT patients, we have so far identified UROD mutations in 86 seemingly unrelated cases. Two mutations made up for some 70% of all Norwegian mutations, viz. IVS6+1G>C (44%) and R193P (27%). The mutation R193P was first described in a single patient by JD Phillips et al in Utah (Blood 2001;98:3179-85), but it has not been reported since. Studies of 17 microsatellite markers in a 9Mb genomic region encompassing the UROD locus, clearly indicated that all R193P mutations found in the Norwegian, as well as the Utah PCT patients, are likely to be identical by descent. It is therefore likely that we are dealing with a Norwegian UROD founder mutation. In preliminary studies, the genetic length of the most common shared haplotype ranged from less than 3.1cM to more than 6.2cM. The results of extended marker studies as well as attempts at genealogical studies, will be presented.