Genetic linkage analysis in familial benign (hypocalciuric) hypercalcemia: evidence for locus heterogeneity

Familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) is characterized by inheritance, in an autosomal dominant pattern, of lifelong hypercalcemia without hypercalciuria, which is often mistaken for classical primary hyperparathyroidism. Recently, the FBH trait was linked, in four families, to chromosome 3q. We report genetic linkage analysis in 140 persons from five additional families having FBH (65 affected, 67 unaffected, and 8 unclassifiable). In four families, FBH mapped to chromosome 3q, between D3S1215 and D3S20, maximum multipoint lod score 12.9. By contrast, in the fifth kindred FBH mapped to chromosome 19p13.3, tightly linked to the marker loci D19S20 and D19S266 (two-point lod score at recombination fraction = .001 is 3.44 and 3.70, respectively). Thus, the FBH phenotype results from mutations at two separate loci on chromosomes 3q and 19p.