Further evidence for genetic heterogeneity within type II autosomal dominant osteopetrosis

Type II autosomal dominant osteopetrosis (ADO II) is characterized by an in creased bone mass that contrasts with the high frequency of fractures. Link age analysis performed in an extensive Danish family recently provided evid ence for the mapping of an ADO II gene to an 8.5-cM region in chromosome 1p 21 between microsatellite markers D1S486 and D1S2792, We recruited, phenoty ped, and haplotyped 4F catheter ADO II families including 18 affected subje cts and 29 unaffected subjects in order to narrow the candidate region and to search for genetic heterogeneity, ADO II diagnosis was ascertained by th e observation of vertebral end plate thickening in at least 2 patients from successive generations. Linkage studies involved five microsatellite marke rs (D1S486, D1S206, D1S495, D1S248, and D1S2792) spanning 1p21, Haplotype a nalyses of two of our families clearly excluded the tested locus. The two r emaining families gave poorly informative results. These results, combined with those previously reported in two American families, suggest that chrom osomal region 1p21 is most likely a minor locus for ADO II.