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)

Angelman syndrome (AS) is characterized by mental retardation, absence of speech, seizures and motor dysfunction. AS is caused by maternal deletions for chromosome 15q11-q13, paternal uniparental disomy (UPD), imprinting defects or loss-of-function mutations in the UBE3A locus which encodes E6-AP ubiquitin-protein ligase. The UBE3A gene is imprinted with paternal silencing in human brain and similar silencing of the Ube3a locus in Purkinje cells and hippocampal neurons in the mouse. We have sequenced the major coding exons for UBE3A in 56 index patients with a clinical diagnosis of AS and a normal DNA methylation pattern. The analysis identified disease-causing mutations in 17 of 56 patients (30%) including 13 truncating mutations, two missense mutations, one single amino acid deletion and one stop codon mutation predicting an elongated protein. Mutations were identified in six of eight families (75%) with more than one affected case, and in 11 of 47 isolated cases (23%); no mutation was found in one family with two siblings, one with a typical and one with an atypical phenotype. Mutations were de novo in nine of the 11 isolated cases. An amino acid polymorphism of threonine substituted for alanine at codon 178 was identified, and a 3 bp length polymorphism was found in the intron upstream of exon 8. In all informative cases, phenotypic expression was consistent with imprinting with a normal phenotype when a mutation was on the paternal chromosome and an AS phenotype when a mutation was on the maternal chromosome. Laboratory diagnosis and genetic counseling for AS are complex, and mutation analysis is valuable in clinically typical AS patients with a normal methylation analysis.
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PMID:The spectrum of mutations in UBE3A causing Angelman syndrome. 988 41

Angelman syndrome (AS) is a neurodevelopmental disorder caused by maternal deficiency of the UBE3A gene that encodes E6-AP ubiquitin-protein ligase. Expression of the UBE3A gene from the maternal chromosome is essential to prevent AS. AS is characterized by severe mental retardation, ataxia, and a defined behavioral pattern characterized mainly by happy/sociable disposition. This study used the Bayley Scales of Infant Development and the Vineland Adaptive Behavior Scales to examine the cognitive abilities and adaptive behavior of children (n = 20) with the four known molecular classes of AS, including patterns of strengths and weaknesses across adaptive behavior domains, and the relationship between adaptive behavior and overall cognitive abilities. Cognitive skills fell within the severe to profound range of mental deficiency. Differences in cognitive skills according to genetic subtype only partially supported previous research and suggest that there is overlap in abilities across genetic subtypes of AS. Adaptive behavior skills were also significantly delayed, with participants demonstrating a significant strength in socialization, and a weakness in motor skills. Strong, positive correlations emerge between cognitive ability scores and adaptive behaviors scores. These results provide further delineation of a cognitive/behavioral phenotype in AS.
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PMID:Cognitive and adaptive behavior profiles of children with Angelman syndrome. 1521 98