FOUNDER EFFECT AT PGL1 IN HEREDITARY HEAD AND NECK PARAGANGLIOMA FAMILIES FROM THE NETHERLANDS

PGL1, a gene responsible for hereditary paragangliomas of the head and neck, recently was mapped to a 2-cM interval on chromosome 11q22-q23, by linkage and haplotype-sharing analysis of a large multibranch Dutc h family. We determined the disease-linked haplotype, as defined by 13 markers encompassing a large interval on 11q21-q23, in 10 additional families ascertained from the same geographical locale. Alleles were i dentical for six contiguous markers, spanning a genetic distance of 6 cM and containing PGL1, Despite this strong indication of a common anc estor, no kinships between the families could be demonstrated through genealogical surveys going back to 1800 A.D. We conclude that a single ancestral mutation is responsible for most, if not all, hereditary pa ragangliomas, in this region of The Netherlands, and that strong found er effects map exist at the PGL1 locus.