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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Persons with Angelman syndrome (AS) have mental retardation, epilepsy, and a characteristic "puppet-like" gait. Behaviorally, they are distinctive because they have no speech and have excessive laughter. A speech and communication evaluation of 7 persons with AS was performed to provide improved understanding of the speech deficit. Assessments included prelanguage and language development, oral motor abilities, and cognitive and social interaction skills. Results indicate that the typical lack of speech may not be due to mental retardation alone. Oral motor dyspraxia, and deficits in social interaction and attention were characteristic of AS and contributed to the lack of speech.
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PMID:Communication, cognition, and social interaction in the Angelman syndrome. 849 32

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation disorders caused by a deficiency of paternal (PWS) or maternal (AS) contributions for chromosome 15 by either deletion or uniparental disomy (UPD). To further study the molecular mechanisms involved in these disorders and to improve molecular diagnostic methods, we have isolated three dinucleotide repeat markers in the PWS/AS critical region. An Alu-CA PCR method was used to isolate CA-repeat markers directly from yeast artificial chromosome (YAC) clones identified by probes IR4-3R (D15S11), LS6-1 (D15S113), and GABAA receptor B3 (GABRB3). Three markers with 6-11 alleles and 73-83% heterozygosities were identified and analyzed by multiplex PCR. Gene-centromere mapping was performed on a panel of ovarian teratomas of known meiotic origin, and showed the most proximal marker, IR4-3R, to be 13 cM (95% confidence limits: 7-19 cM) from the centromere of chromosome 15. Molecular diagnostic studies were performed on 20 PWS and 9 AS patients. In 17 patients with deletions, the parental origin of deletion was determined. Ten PWS patients were shown to have maternal heterodisomy. Since these markers are only 13 cM from the centromere, heterodisomy indicates that maternal meiosis I nondisjunction is involved in the origin of UPD. In contrast, two paternal disomy cases of AS showed isodisomy for all markers tested along the length of chromosome 15. This suggests a paternal meiosis II nondisjunction event (without crossing over) or, more likely, monosomic conception (due to maternal nondisjunction) followed by chromosome duplication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiplex PCR of three dinucleotide repeats in the Prader-Willi/Angelman critical region (15q11-q13): molecular diagnosis and mechanism of uniparental disomy. 849 3

Genes for Prader Willi syndrome/Angelman syndrome are homologous to genes for fragile X syndrome. Genetic imprinting and expanded trinucleotide repeats cause mental retardation, autism and aggression.
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PMID:Genes for Prader Willi syndrome/Angelman syndrome and fragile X syndrome are homologous, with genetic imprinting and unstable trinucleotide repeats causing mental retardation, autism and aggression. 891 Aug 78

Angelman syndrome (AS) is a relatively frequent disorder of psychomotor development caused by loss of function of a gene from chromosome 15q11-q13, a region subject to genomic imprinting. The AS gene(s) is exclusively expressed from the maternal chromosome. Several kinds of mutations have been found to cause AS. More than half of the cases exhibit a deletion of the maternal 15q11-q13 region. Recently, we and others described a new mutation type, the imprinting mutation, characterised by normal, biparental inheritance but aberrant methylation patterns of the entire chromosomal region. In AS, a paternal imprint is found on the maternal chromosome probably leading to functional inactivation of the AS gene(s). We have now compared the phenotype of 9 AS patients with imprinting mutation to that of nine age-matched ones with a maternally derived deletion. Both groups were evaluated for 19 common AS symptoms. All patients, independently of their molecular findings, showed classical AS symptoms such s mental retardation, delayed motor development, and absent speech. In contrast, for two signs, hypopigmentation and microcephaly, a different distribution among both groups was observed. Only one of nine AS patients with an imprinting mutation, but seven of nine in the deletion control group showed either symptom. Our results suggest that imprinting mutations, in contrast to deletions, cause only incomplete loss of gene function or that maternally derived deletions affect also genes not subject to genomic imprinting. We conclude that AS is caused by loss of function of a major gene that is imprinted but that there are also other genes that contribute to the phenotype when in hemizygous condition.
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PMID:Phenotypic differences in Angelman syndrome patients: imprinting mutations show less frequently microcephaly and hypopigmentation than deletions. 895 35

Angelman syndrome (AS), characterized by mental retardation, seizures, frequent smiling and laughter, and abnormal gait, is one of the best examples of human disease in which genetic imprinting plays a role. In about 70% of cases, AS is caused by de novo maternal deletions at 15q11-q13 (ref. 2). Approximately 2% of AS cases are caused by paternal uniparental disomy (UPD) of chromosome 15 (ref. 3) and 2-3% are caused by "imprinting mutations'. In the remaining 25% of AS cases, no deletion, uniparental disomy (UPD), or methylation abnormality is detectable, and these cases, unlike deletions or UPD, can be familial. These cases are likely to result from mutations in a gene that is expressed either exclusively or preferentially from the maternal chromosome 15. We have found that a 15q inversion inherited by an AS child from her normal mother disrupts the 5' end of the UBE3A (E6-AP) gene, the product of which functions in protein ubiquitination. We have looked for novel UBE3A mutations in nondeletion/non-UPD/non-imprinting mutation (NDUI) AS patients and have found one patient who is heterozygous for a 5-bp de novo tandem duplication. We have also found in two brothers a heterozygous mutation, an A to G transition that creates a new 3' splice junction 7 bp upstream from the normal splice junction. Both mutations are predicted to cause a frameshift and premature termination of translation. Our results demonstrate that UBE3A mutations are one cause of AS and indicate a possible abnormality in ubiquitin-mediated protein degradation during brain development in this disease.
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PMID:UBE3A/E6-AP mutations cause Angelman syndrome. 898 71

A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome.
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PMID:Robertsonian (15q;15q) translocation in a child with Angelman syndrome: evidence of uniparental disomy. 898 60

The diagnosis of Angelman syndrome has seldom been made in infancy because the typical craniofacial dysmorphism and the typical outbursts of unprovoked laughter are not fully developed before the second and third year of life. Other features such as mental retardation or absence of language, though invariably present, are less obvious in the first year of life. We describe three children in whom consecutive electroencephalographic (EEG) studies show very large amplitude slow activity at 2-3/s, often rhythmic, usually occurring in prolonged runs and often more prominent posteriorly, sometimes with spikes or sharp-wave activity, and invariably associated with a diffuse rhythmic activity at 4-6/ s of 200 microvolts. The changes were present as early as six months of life. They preceded development of seizure and occurred much earlier than the craniofacial dysmorphology. It is concluded that methodical use of EEG in the elucidation of children with developmental disorder and knowledge of the characteristic EEG picture may help to identify patients with Angelman syndrome at an early age and before the clinical features become obvious.
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PMID:[EEG and early diagnosis of Angelman syndrome]. 907 74

The most common of the heterogeneous group of the extra structurally abnormal chromosomes (ESACs) is the inv dup(15), whose presence results in tetrasomy 15p and partial tetrasomy 15q. Inv dup(15), containing the Prader-Willi/Angelman syndrome (PWS/AS) region, are constantly associated with phenotypic abnormalities and mental retardation. We report on four additional patients with inv dup(15), whose behavioral pattern, and neurologic and physical findings further delineate the phenotype of this neurogenetic syndrome. We also provide FISH analyses on chromosomes of the observed ESACs and discuss the role of a number of genes located within the tetrasomic region.
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PMID:The inv dup(15) syndrome: a clinically recognizable syndrome with altered behavior, mental retardation, and epilepsy. 910 4

Angelman syndrome (AS) is a human genetic disorder characterized by mental retardation, seizures, inappropriate laughter, abnormal galt, tremor and ataxia. There is strong genetic evidence that the disorder is associated with a maternally expressed, imprinted gene mapping to chromosome 15q11-13. Affected patients demonstrate varied molecular abnormalities, including large maternal deletions, uniparental paternal disomy (UPD). Imprinting mutations and loss of function mutations of E6-associated-protein (E6-AP) ubiquitin-protein ligase (UBE3A). All of these abnormalities are associated with loss of maternal expression of UBE3A. Although mutations in UBE3A cause AS, indicating that maternal-specific expression of UBE3A is essential for a normal phenotype, evidence for maternal-specific expression of UBE3A has been lacking. Using mice with partial paternal UPD encompassing Ube3a to differentiate maternal and paternal expression, we found by in situ hybridization that expression of Ube3a in Purkinje cells, hippocampal neurons and mitral cells of the olfactory bulb in UPD mice was markedly reduced compared to non-UPD littermates. In contrast, expression of Ube3a in other regions of the brain was only moderately or not at all reduced in UPD mice. The major phenotypic features of AS correlate with the loss of maternal-specific expression of Ube3a in hippocampus and cerebellum as revealed in the mouse model.
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PMID:Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. 928 1

DNA mapping studies in two families provide further information on the Angelman syndrome critical region, which has recently been defined by the gene UBE3A. The first family has probable familial Angelman syndrome with a maternally imprinted inheritance pattern. A 5 year old girl with this disorder has a 14 year old brother and an 11 year old male cousin who have less typical clinical features. DNA microsatellite analysis has shown that the three share a common segment of the same grandpaternal chromosome 15q11-q13 that overlaps with UBE3A. The child with typical Angelman syndrome has an additional maternal recombination 5' to UBE3A. The second family is a mother and son both of whom have mental retardation but no other features of Angelman syndrome despite an extensive DNA deletion on the telomeric side of UBE3A. Together, the two families identify a region between loci D15S210 and D15S986 which forms part of the Angelman syndrome critical region. A new microsatellite (D15S1234) is described which can be used in place of the LS6-1 marker at locus D15S113.
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PMID:The elusive Angelman syndrome critical region. 932 55


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