Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rett syndrome (RTT), caused by mutations in MECP2 (encoding methyl CpG binding protein 2), and Angelman syndrome (AS), caused by maternal deficiency of chromosome 15q11-13, are autism-spectrum neurodevelopmental disorders. MeCP2 is a transcriptional repressor of methylated genes, but MECP2 mutation does not directly affect the imprinted expression of genes within 15q11-13. We tested a potential role for MeCP2 in the homologous pairing of imprinted 15q11-13 alleles in human brain tissue and differentiated neurons by fluorescence in situ hybridization (FISH). FISH analysis of control cerebral samples demonstrated a significant increase in homologous pairing specific to chromosome 15 from infant to juvenile brain samples. Significant and specific deficiencies in the percentage of paired chromosome 15 alleles were observed in RTT, AS and autism brain samples when compared with normal controls. SH-SY5Y neuroblastoma cells also showed a significant and specific increase in the percentage of chromosome 15q11-13 paired alleles following induced differentiation in vitro. Transfection with a methylated oligonucleotide decoy specifically blocked binding of MeCP2 to the SNURF/SNRPN promoter within 15q11-13 and significantly lowered the percentage of paired 15q11-13 alleles in SH-SY5Y cells. These combined results suggest a role for MeCP2 in chromosome organization in the developing brain and provide a potential mechanistic association between several related neurodevelopmental disorders.
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PMID:Homologous pairing of 15q11-13 imprinted domains in brain is developmentally regulated but deficient in Rett and autism samples. 1568 52

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are considered sister imprinting disorders. Although both AS and PWS congenital neurodevelopmental disorders have chromosome 15q11.3-q13 dysfunction, their molecular mechanisms differ owing to genomic imprinting, which results in different parent-of-the-origin gene expressions. Recently, several randomized controlled trials have been proceeded to treat specific symptoms of AS and PWS. Due to the advance of clinical management, early diagnosis for patients with AS and PWS is important. PWS is induced by multiple paternal gene dysfunctions, including those in MKRN3, MAGEL2, NDN, SNURF-SNPRPN, NPAP1, and a cluster of small nucleolar RNA genes. PWS patients exhibit characteristic facial features, endocrinological, and behavioral phenotypes, including short and obese figures, hyperphagia, growth hormone deficiency, hypogonadism, autism, or obsessive- compulsive-like behaviors. In addition, hypotonia, poor feeding, failure to thrive, and typical facial features are major factors for early diagnosis of PWS. For PWS patients, epilepsy is not common and easy to treat. Conversely, AS is a single-gene disorder induced by ubiquitin-protein ligase E3A dysfunction, which only expresses from a maternal allele. AS patients develop epilepsy in their early lives and their seizures are difficult to control. The distinctive gait pattern, excessive laughter, and characteristic electroencephalography features, which contain anterior-dominated, high-voltage triphasic delta waves intermixed with epileptic spikes, result in early suspicion of AS. Often, polytherapy, including the combination of valproate, levetiracetam, lamotrigine, and benzodiazepines, is required for controlling seizures of AS patients. Notably, carbamazepine, oxcarbazepine, and vigabatrin should be avoided, since these may induce nonconvulsive status epilepticus. AS and PWS presented with distinct clinical manifestations according to specific molecular defects due to genomic imprinting. Early diagnosis and teamwork intervention, including geneticists, neurologists, rehabilitation physicians, and pulmonologists, are important. Epilepsy is common in patients with AS, and after proper treatment, seizures could be effectively controlled in late childhood or early adulthood for both AS and PWS patients.
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PMID:Clinical characteristics and epilepsy in genomic imprinting disorders: Angelman syndrome and Prader-Willi syndrome. 3226 45