Objectives: The rarity of familial neuroblastoma (NB) has allowed only a few linkage studies, most of which did not show any evidence of linkage to regions involved in somatic alterations or to genes implicated in other neurocristopathies seldom associated with NB. We screened a highly informative family with recurrent NB by genome-wide linkage analysis aimed at identifying chromosomal regions for NB predisposing genes.
Methods: A genome-wide screen was performed using 382 microsatellite markers. Multipoint model-based linkage analysis was carried out under a dominant mode of inheritance for the disease using the 'affected only' approach.
Results: Our analysis identified two haplotypes co-segregating with the disease on chromosomes 2p and 12p, and yielded maximum lod-score values of 3.01 (p < 0.0001) for markers on both intervals.
Conclusions: Evidence of linkage was reported at 16p in North American families, whereas our studies excluded this interval and indicated other loci for disease predisposition, thus confirming the remarkable genetic heterogeneity of NB. These results suggest an oligogenic inheritance in NB involving more loci in genetic determination of the disease.