ALBRIGHT HEREDITARY OSTEODYSTROPHY AND DEL(2)(Q37.3) IN 4 UNRELATED INDIVIDUALS

Albright hereditary osteodystrophy (AHO) is a condition with character istic physical findings (short stature, obesity, round face, brachydac tyly) but variable biochemical changes (pseudohypoparathyroidism, pseu dopseudohypoparathyroidism). Most patients with AHO have decreased act ivity of the guanine nucleotide-binding protein (G(s) protein) that st imulates adenylyl cyclase. The gene encoding the alpha subunit of the G(s) protein (GNAS1) has been mapped to the long arm of chromosome 20. We describe 4 unrelated individuals with apparent AHO, associated wit h small terminal deletions of chromosome 2. All 4 patients had normal serum calcium levels consistent with pseudopseudohypoparathyroidism. D el(2)(q37) is the first consistent karyotypic abnormality that has bee n documented in AHO [Phelan et al., 1993: Am J Hum Genet 53:484]. The finding of the same small terminal deletion in 4 unrelated individuals with a similar phenotype suggests that a gene-locus in the 2q37 regio n is important in the pathogenesis of Albright syndrome. The associati on of Albright syndrome and the GNAS1 locus on chromosome 20 is well d ocumented. The observation of a second potential disease locus on chro mosome 2 may help explain the heterogeneity observed in this disorder. (C) 1995 Wiley-Liss, Inc.