Short Fourth and Fifth Metacarpals
Division of Internal Medicine, Department of Medicine, Cooper University Hospital, UMDNJ-Robert Wood Johnson Medical School, Education & Research Bldg, Third Floor, Camden, NJ 08103, USA.JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 09/2012; 308(10):1034-5. DOI: 10.1001/2012.jama.11065
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ABSTRACT: The GNAS locus on chromosome 20q13.11 is the archetypal complex imprinted locus. It comprises a bewildering array of alternative transcripts determined by differentially imprinted promoters which encode distinct proteins. It also provides the classic example of tissue-specific imprinted gene expression, in which the canonical GNAS transcript coding for Gsalpha is expressed predominantly from the maternal allele in a set of seemingly unrelated tissues. Functionally, this rather obscure imprinting is nevertheless of considerable clinical significance, as it dictates the nature of the disease caused by inactivating mutations in Gsalpha, with end organ hormone resistance specifically on maternal transmission (pseudohypoparathyroidism type 1a, PHP1a). In addition, there is a bona fide imprinting disorder, PHP1b, which is caused specifically by DNA methylation defects in the differentially methylated regions (DMRs) that determine tissue-specific monoallelic expression of GNAS. Although the genetic defect in PHP1a and the disrupted imprinting in PHP1b both essentially result in profound reduction of Gsalpha activity in tissues with monoallelic GNAS expression, and despite a growing awareness of the overlap in these two conditions, there are important pathophysiological differences between the two whose basis is not fully understood. PHP1b is one of the only imprinted gene syndromes in which cis-acting mutations have been discovered that disrupt methylation of germline-derived imprint marks; such imprinting mutations in GNAS are helping to provide important new insights into the mechanisms of imprinting establishment generally.American Journal of Medical Genetics Part C Seminars in Medical Genetics 08/2010; 154C(3):377-86. DOI:10.1002/ajmg.c.30271 · 3.54 Impact Factor
Article: Imprints of disease at GNAS1Journal of Clinical Investigation 05/2001; 107(7):793-4. DOI:10.1172/JCI12645 · 13.77 Impact Factor
- Journal of Bone and Mineral Research 09/1999; 14(8):1255-60. DOI:10.1359/jbmr.1918.104.22.1685 · 6.59 Impact Factor
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