Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alternatively spliced GNAS1 and XL-GNAS1, encoding respectively the stimulatory G-protein alpha-subunit (Gsalpha) and the extra-large stimulatory G-protein alpha-subunit (XLsalpha), are located on the imprinted chromosomal region 20q13.12-13. We presently report a functional polymorphism in the imprinted XL-GNAS1 gene. In three patients, a 36 bp insertion and two basepair substitutions flanking this insertion were found in the paternally inherited XL-GNAS1 exon 1. They clinically manifest an enhanced trauma-related bleeding tendency and a variable degree of mental retardation. A platelet aggregation inhibition test to evaluate Gs function was developed. Their platelets display Gs hyperfunction and an enhanced cAMP generation upon stimulation of Gs-coupled receptors. The prevalence of the XLsalpha insertion in a normal control group was 2.2%. Normal controls, inheriting the insertion maternally, had a normal platelet Gs activity, whereas controls inheriting the insertion paternally had increased inducible platelet Gs activity, defining the insertion as a functional polymorphism. This paternally inherited XLsalpha insertion represents a new genetic cause of an inherited bleeding tendency, although to a variable degree.
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PMID:Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding. 1158 2

Albright hereditary osteodystrophy (AHO) results from heterozygous inactivation of G(s)alpha, encoded by the GNAS1 locus on the distal long arm of chromosome 20. This autosomal dominant condition is characterized by short stature, obesity, shortening of the metacarpals and metatarsals, and variable mental retardation and may also include end-organ resistance to multiple hormones. Small insertions and deletions or point mutations of GNAS1 are found in approximately 80% of patients with AHO. The remainder may be accounted for by larger genomic rearrangements, but none have been reported to date. We now describe two patients with constitutional 20q deletions and features of AHO. Such deletions are rare in the published literature and have not previously been associated with AHO. Molecular genetic analysis confirmed complete deletion of GNAS1 in both patients. Parental origin could be determined in both cases and provides further support for the parent-of-origin effect on the biochemical status of patients with AHO.
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PMID:Constitutional deletion of chromosome 20q in two patients affected with albright hereditary osteodystrophy. 1240 7

Osteoma cutis is a condition characterized by theformation of bone within the skin. Such aberrantossification of the skin and subcutaneous tissue isconsidered primary when it arises in the absence ofunderlying tissue damage or a preceding cutaneouslesion. Conversely, secondary osteoma cutis occurswhen skin ossification is the result of a pre-existingskin lesion, trauma, or inflammatory process [1,2].Although rare, primary osteoma cutis has beenassociated with a number of different geneticdisorders. Albright hereditary osteodystrophy (AHO),a condition first described in 1942 by Fuller Albright,is an autosomal dominant metabolic disorder causedby a mutation in the GNAS1 gene [3]. This disease isassociated with a variety of phenotypic traits includingcutaneous ossification, short stature, brachydactyly,obesity, and mental retardation. It should be notedthat brachydactyly is the most specific feature of AHO[4]. However, owing to variable expressivity individualsmay present only with a subset of these symptoms [5,6]. The cutaneous ossification observed in patientswith AHO may be seen in infancy or early childhoodand is sometimes the earliest presenting symptom.Nonetheless, because clinical features of AHO canbe seen in the absence of metabolic derangements(i.e. normal serum calcium, phosphorus, and PTHlevels) an early diagnosis is often missed and delayedfor many years. Herein, we present a case of miliaryosteoma cutis of the face in a 68 year-old woman withphenotypic features of AHO and laboratory studiesconsistent with type 1a PHP.
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PMID:Multiple miliary osteoma cutis of the face associated with Albright hereditary osteodystrophy in the setting of acne vulgaris: a case report. 2832 22