Genetics of pseudohypoparathyroidism

Weinstein, Lee S. and Chen, Min and Liu, Jie (2004) Genetics of pseudohypoparathyroidism. Clinical cases in mineral and bone metabolism, 1 (2). pp. 117-122. ISSN 1971-3266

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Abstract

Pseudohypoparathyroidism (PHP) is a group of disorders defined by the presence of renal parathyroid hormone (PTH) resistance, resulting in biochemical hypoparathyroidism in the presence of elevated serum PTH levels. Most PHP patients have diminished urinary cyclic AMP responses to administered PTH, indicating a defect in proximal PTH signaling. Heterozygous inactivating mutations of Gs , the G protein which couples hormone and other receptors to intracellular cyclic AMP production, lead to Albright hereditary osteodystrophy (AHO), a disorder characterized by skeletal defects, short stature, obesity, and neurobehavioral defects. Maternal inheritance of Gs m u t ations leads to both AHO and resistance to multiple hormones, including PTH, a condition referred to as PHP type 1a. In contrast, paternal inheritance of the same mutations leads to AHO alone. This is because Gs is imprinted in a tissue-specific manner, and is poorly expressed from the paternal allele in various tissues, including renal proximal tubules. PHP type 1b patients have renal PTH resistance in the absence of AHO resulting from imprinting defects of the Gs gene (G N A S) in which both parental alleles have a paternal-specific imprinting pattern. The maternal imprint is lost in one specific region located just upstream of the Gs promoter, which likely leads to Gs d e f iciency in specific tissues (such as proximal tubules) where Gs is normally expressed primarily from the maternal allele. Familial PHP type 1b is also associated with a deletion mutation upstream of G N A S within a region presumed to be important for G N A S imprinting. This mutation only leads to a G N A S i m p r i n ting defect and PTH resistance when it is inherited maternally

Item Type:	Article
Uncontrolled Keywords:	Pseudohypoparathyroidism, genomic imprinting, G protein, cyclic AMP
Subjects:	600 Tecnologia - Scienze applicate > 610 Medicina e salute (Classificare qui la tecnologia dei servizi medici) > 616 Malattie (classificare qui la Clinica medica, la medicina basata sull'evidenza, la Medicina interna, la Medicina sperimentale) > 616.7 Malattie del sistema muscoloscheletrico
Depositing User:	Danilo Dezzi
Date Deposited:	18 Apr 2014 13:17
Last Modified:	18 Apr 2014 13:17
URI:	http://eprints.bice.rm.cnr.it/id/eprint/8746

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