ABSTRACT
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 Gsα 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.
KEYWORD
Albright's hereditary osteodystrophy - pseudohypoparathyroidism - Gs alpha - GNAS1
- imprinting
