Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudohypoparathyroidism type I is a hereditary disorder characterized by resistance to parathyroid hormone and other hormones that work via cyclic adenosine 3', 5'-monophosphate (cAMP). Most patients with this disorder have generalized deficient activity of Ns-protein (type Ia), which couples stimulatory hormone receptors to catalytic adenylate cyclase. In patients with normal Ns-protein activity (type Ib), a decreased incidence of resistance to hormones other than parathyroid hormone exists. Mental deficiency of unknown cause occurs in 47% to 75% of all patients with pseudohypoparathyroidism type I. Because mutations in the adenylate cyclase-cAMP system may affect the learning ability of Drosophila flies, we assessed mental deficiency in 25 patients whose Ns-protein activity we had determined: 9 of 14 patients with type Ia disorder and 0 of 11 patients with type Ib disorder had mental deficiency. We suggest that Ns-protein deficiency, reduced cAMP levels, or both, are involved in the mental deficiency in these patients and probably in mental function in humans.
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PMID:Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency. 308 87

Primary lysosome-associated membrane protein-2 (LAMP-2) deficiency is an X-linked disease, characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and mental retardation, previously known as Danon disease. Mutations of lamp-2 gene have been reported so far in about 20 patients, one of whom was Italian. We describe a new Italian case with persistent hyperCKemia, exercise intolerance and hypertrophic cardiomyopathy but with no muscle weakness or mental impairment. Muscle biopsy revealed a vacuolar myopathy with mild glycogen storage, and immunohistochemical studies detected LAMP-2 deficiency. A new nucleotide substitution (T961C) on exon 8 of lamp-2 gene was identified as responsible for the protein deficiency. This is the first missense mutation so far described. LAMP-2 deficiency should be considered as a cause of recurrent hyperCKemia and hypertrophic cardiomyopathy.
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PMID:Asymptomatic hyperCKemia in a case of Danon disease due to a missense mutation in Lamp-2 gene. 1590 87

Danon disease, an X-linked dominant disorder, results from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene and presents with hypertrophic cardiomyopathy, skeletal myopathy, and mental retardation. To investigate the effects of LAMP2 gene mutations on protein expression in different tissues, we screened LAMP2 gene mutations and LAMP-2 protein deficiency in the skeletal muscle of nine unrelated patients with hypertrophic cardiomyopathy and vacuolar myopathy. We identified three novel families (including one affected mother) with unreported LAMP2 gene null mutations and LAMP-2 protein deficiency in skeletal and myocardial muscle, leukocytes, and fibroblasts. LAMP-2 protein deficiency was detectable in various tissues, including leukocytes, explaining the multisystem clinical involvement. Skeletal muscle immunopathology showed that mutant protein was not localized in the Golgi complex, vacuolar membranes expressed sarcolemmal-specific proteins, and the degree of muscle fiber vacuolization correlated with clinical muscle involvement. In our female patient, muscle histopathology and LAMP-2 protein analysis was inconclusive, indicating that diagnosis in females requires mutation identification. The random X-chromosome inactivation found in muscle and leukocytes excluded the possibility that selective involvement of some tissues in females is due to skewed X-chromosome inactivation. Therefore, biochemical analysis of leukocytes might be used for screening in male patients, but genetic screening is required in females.
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PMID:Generalized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease. 1656 4