Genetic basis for resistance to parathyroid hormone.
Pseudohypoparathyroidism (PHP) is associated with biochemical hypoparathyroidism (i.e. hypocalcemia and hyperphosphatemia) due to parathyroid hormone (PTH) resistance rather than to PTH deficiency. Patients with PHP type 1a have a generalized form of hormone resistance plus a constellation of developmental defects termed Albright hereditary osteodystrophy (AHO). Within PHP type 1a families some individuals will show AHO but have normal hormone responsiveness, a variant phenotype termed pseudo-PHP. By contrast, patients with PHP type 1b manifest only PTH resistance and lack features of AHO. These various forms of PHP are due to defects in the GNAS1 gene that lead to decreased expression or activity of the alpha-subunit of the stimulatory G protein (G(s)alpha). Tissue-specific genomic imprinting of GNAS1 accounts for the variable phenotypes of patients with GNAS1 defects.
Levine
Michael A
MA
The Children's Hospital at The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. levinem@ccf.org
Germain-Lee
Emily
E
Jan de Beur
Suzanne
S
D000818:Animals; D000242:Cyclic AMP / Q000652:urine; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D018392:Genomic Imprinting; D006801:Humans; D020125:Mutation, Missense; D010281:Parathyroid Hormone / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
D010281:Parathyroid Hormone; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs