Albright's hereditary osteodystrophy and pseudohypoparathyroidism.
Pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO) are not interchangeable terms. AHO describes a constellation of physical features, including short adult stature, obesity, brachydactyly, and ectopic ossifications. PHP means end-organ resistance to PTH and is subclassified into types Ia, Ib, and Ic and type II. Pseudopseudohypoparathyroidism (PPHP) is a term used for individuals with AHO who have normal end-organ responses to PTH. Both the PHPIa and PPHP forms of AHO result from heterozygous deactivating mutations in the GNAS1 gene associated with a 50% reduction in bioactivity of the Gsalpha protein that it encodes. The GNAS1 gene is subject to tissue-specific genomic imprinting. Patients with mutations on their maternally derived allele are likely to have associated PHPIa, whereas mutations on the paternal allele usually cause PPHP. Isolated PTH resistance (PHPIb) can result from mutations within the GNAS1 gene but is more commonly caused by epigenetic imprinting abnormalities affecting the upstream exon 1A. The causes of PHP type Ic and PHP type II are not yet clear, and the latter is likely to be heterogeneous.
Wilson
Louise C
LC
Clinical and Molecular Genetics Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK. l.wilson@ich.ucl.ac.uk
Hall
Christine M
CM
D003937:Diagnosis, Differential; D005359:Fibrous Dysplasia, Polyostotic / Q000000981:diagnostic imaging / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000000981:diagnostic imaging / Q000235:genetics*; D011859:Radiography
D019205:GTP-Binding Protein alpha Subunits, Gs