Incidence of 15q deletions in the Angelman syndrome: A survey of twelve affected persons

Williams, Charles A.; Gray, Brian A.; Hendrickson, Jill E.; Stone, John W.; Cantú, Eduardo S.

doi:10.1002/ajmg.1320320313

Cited by 80 publications

(35 citation statements)

References 25 publications

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“…EEG abnormalities have been reported to improve with age, showing diminution of seizure discharges after puberty [Matsumoto et al, 1992;Clayton-Smith, 1993]. Whenever it had been performed, the EEG was abnormal in the published reports of older patients [Buntinx et al, 1995;Bjerre, 1984;Williams et al, 1989]. All of our patients had an abnormal EEG.…”

Section: Neurobehavioural Aspectsmentioning

confidence: 44%

“…Several reports describe adult patients [Smith et al, 1989;Magenis et al, 1990;Williams et al, 1989;Reish and King, 1995] with the oldest being a male, age 76 years [Bjerre et al, 1984]. A review of 6 patients over 20 years old [Penner et al, 1993] and a review of 18 cases older than 16 years [Buntinx et al, 1995] provide information on aspects of the adult phenotype.…”

Section: Resultsmentioning

confidence: 95%

“…Many subsequent reports largely comprise descriptions of children [Clayton-Smith and Pembrey, 1992] of importance for early diagnosis [Fryburg et al, 1991]. The phenotype consists of flat occiput, posterior occipital groove, small widely spaced teeth, deep set eyes, midface hypoplasia, large mouth, and prognathism together with a happy disposition with frequent outbursts of inappropriate laughter [Williams et al, 1989;Clayton-Smith and Pembrey, 1992;Williams et al, 1995]. Other signs are ataxia, flapping of the hands when walking, absent speech, microcephaly, severe development disability, and an abnormal EEG pattern [Boyd et al, 1988].…”

Section: Introductionmentioning

confidence: 97%

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Manifestations in institutionalised adults with Angelman syndrome due to deletion

Sandanam

Beange²,

Robson³

et al. 1997

Am. J. Med. Genet.

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Undiagnosed institutionalised patients were reviewed in an attempt to identify those with Angelman syndrome (AS). The aim was to test these patients for deletion of chromosome 15(q11-13) and to describe the adult phenotype. The selection criteria included severe intellectual disability, ataxic or hypermotoric limb movements, lack of speech, a "happy" demeanour, epilepsy, and facial appearance consistent with the diagnosis. Patients were examined, medical records perused, and patients' doctors contacted as required. Genetic tests performed included routine cytogenetics, DNA methylation analysis (with probe PW71B), and fluorescence in situ hybridisation (with probes D15S10, GABRbeta3, or SNRPN). A deletion in the AS region was detected in 11 patients (9 males and 2 females) of 22 tested. The mean age at last review (March 1996) was 31.5 years (range 24 to 36 years). Clinical assessment documented findings of large mouth and jaw with deep set eyes, and microcephaly in nine patients (two having a large head size for height). No patient was hypopigmented; 1/11 patients was fair. Outbursts of laughter occurred in all patients but infrequently in 7/11 (64%) and a constant happy demeanour was present in 5/11 (46%). All had epilepsy, with improvement in 5/11 (46%), no change in 4 (36%), and deterioration in 2 (18%). The EEG was abnormal in 10/10 patients. Ocular abnormalities were reported in 3/8 patients (37.5%) and 4/11 (36%) had developed kyphosis. Two had never walked. All nine who walked were ataxic with an awkward, clumsy, heavy, and/or lilting gait. No patient had a single word of speech but one patient could use sign language for two needs (food and drink). Our data support the concept that AS resulting from deletion is a severe neurological syndrome in adulthood. The diagnosis in adults may not be straightforward as some manifestations change with age. Kyphosis and keratoconus are two problems of older patients.

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Section: Neurobehavioural Aspectsmentioning

confidence: 44%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Manifestations in institutionalised adults with Angelman syndrome due to deletion

Sandanam

Beange²,

Robson³

et al. 1997

Am. J. Med. Genet.

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5][6][7][8][9][10][11][12] (2,3). Interestingly, similar deletions are found in "50% of patients with Angelman syndrome (AS) (4)(5)(6)(7)(8). AS is characterized by mental retardation, jerky movements, paroxysms of laughter, protruding tongue, a characteristic facial appearance, microcephaly, and an abnormal electroencephalogram pattern (9).…”

mentioning

confidence: 99%

A putative gene family in 15q11-13 and 16p11.2: possible implications for Prader-Willi and Angelman syndromes.

Buiting

Greger

Brownstein

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The genetic defects in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) map to 15q11-13. Using microdissection, we have recently isolated several DNA probes for the critical region. Here we report that microclone MN7 detects multiple loci in 15q11-13 and 16p11.2. Eight yeast artificial chromosome (YAC) clones, two genomic phage clones, and two placenta cDNA clones were isolated to analyze these loci in detail. Two of the YAC clones map to 16p. Six YAC clones and two genomic phage clones contain a total of four or five different MN7 copies, which are spread over a large distance within 15q11-13. One cDNA clone is from chromosome 15 and one is from chromosome 16. The chromosome 15 cDNA detects transcripts of 14 and 8 kilobases in various human tissues. The presence of multiple copies of the MN7 gene family in proximal 15q may conceivably be related to the instability of this region and thus to the etiology of associated disorders.

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“…Since then, over 400 patients have been reported. High-resolution banding analysis showed a deletion of the maternal chromosome 15q11-13 in approximately 60% of Angelman syndrome (AS) patients [Knoll et al, 1989;Williams et al, 1989]. Using molecular techniques, abnormalities can be detected in this same region in about 80% of AS patients: a small percentage of AS patients have a paternal uniparental disomy or imprinting center mutations [Knoll et al, 1990[Knoll et al, , 1991Buiting et al, 1995].…”

Section: Introductionmentioning

confidence: 98%

Angelman syndrome without detectable chromosome 15q11-13 anomaly: Clinical study of familial and isolated cases

et al. 1998

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The clinical findings in 12 Angelman syndrome (AS) patients (4 sib pairs and 4 sporadic cases, aged 12-55 years) without a cytogenetic or molecular detectable defect at the AS locus were compared to those of 28 AS patients (aged 11-50 years) with a deletion, in order to determine whether the clinical spectrum differed between the two groups. There were only two minor differences, i.e., mandibular prognathism was always found in the patients with a defect (100% vs. 58%), whereas truncal hypotonia was found less frequently in the group with a detectable genetic defect (54% vs. 91%). All other clinical and physical characteristics were equally represented in the two groups. Epileptic seizures occurred in 93% and 75%, respectively, of patients with and without a detectable chromosome 15 defect. Specific EEG patterns were found in 90% of both groups. The clinical signs and symptoms of our patients closely resemble those in familial AS cases reported in the literature, with the exception of scoliosis, which was present in 55% of the patients in our study. We conclude that the absence of a detectable cytogenetic or molecular defect at the AS locus is not associated with a strikingly different AS phenotype, compared to those with such a defect. Mutation analysis of the UBE3A gene in our patients without a detectable genetic defect, especially in the familial cases, is currently underway.

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Incidence of 15q deletions in the Angelman syndrome: A survey of twelve affected persons

Cited by 80 publications

References 25 publications

Manifestations in institutionalised adults with Angelman syndrome due to deletion

Manifestations in institutionalised adults with Angelman syndrome due to deletion

A putative gene family in 15q11-13 and 16p11.2: possible implications for Prader-Willi and Angelman syndromes.

Angelman syndrome without detectable chromosome 15q11-13 anomaly: Clinical study of familial and isolated cases

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