HOMOZYGOSITY AND LINKAGE-DISEQUILIBRIUM MAPPING OF THE SYNDROME OF CONGENITAL HYPOPARATHYROIDISM, GROWTH AND MENTAL-RETARDATION, AND DYSMORPHISM TO A 1-CM INTERVAL ON CHROMOSOME 1Q42-43

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, auto somal recessive, congenital disorder with severe, often fatal conseque nces. Since the syndrome is very rare, with all parents of affected in dividuals being consanguineous, it is presumed to be caused by homozyg ous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Ana lysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fr action of 0. Analysis of three additional markers-GGAA6F06, D1S2678, a nd D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genet ic linkage disequilibrium and place the HRD locus within an similar to 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.