LINKAGE STUDIES IN A KINDRED FROM OKLAHOMA, WITH FAMILIAL BENIGN (HYPOCALCIURIC) HYPERCALCEMIA (FBH) AND DEVELOPMENTAL ELEVATIONS IN SERUM PARATHYROID-HORMONE LEVELS, INDICATE A 3RD LOCUS FOR FBH

A five-generation kindred (19 affected, two obligate carriers and 20 u naffected) from Oklahoma USA, in which familial benign (hypocalciuric) hypercalcaemia (FBH) was associated with a developmental elevation in serum parathyroid hormone (PTH) levels, has been investigated for lin kage to the candidate chromosomal regions 3q21-q24 and 19p13.3, 11q13, and 11p15, to which the genes for FBH, multiple endocrine neoplasia t ype 1 (MEN1) and PTH have been mapped respectively. By means of 17 pol ymorphic markers from these regions, linkage was excluded [LOD scores < -2.00 at (theta) = 0.05-0.25]. In addition, an analysis of multipoin t crossovers and use of the LINKMAP program confirmed the exclusion fr om these regions. Thus, this form of FBH, designated the Oklahoma vari ant FBH(Ok), is not linked to markers that segregate with FBH, MEN1 an d PTH; our results indicate further genetic heterogeneity and the pres ence of a third locus for FBH.