Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype? (original) (raw)
1994, American Journal of Medical Genetics
The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age-dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region qll-q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late-onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients.
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Paternal UPD15: Further genetic and clinical studies in four Angelman syndrome patients
American Journal of Medical Genetics, 2000
Among 25 patients diagnosed with Angelman syndrome, we detected 21 with deletion and 4 with paternal uniparental disomy (UPD), 2 isodisomies originating by postzygotic error, and 1 MII nondisjunction event. The diagnosis was obtained by molecular techniques, including methylation pattern analysis of exon 1 of SNRPN and microsatellite analysis of loci within and outside the 15q11-q13 region. Most manifestations present in deletion patients are those previously reported. Comparing the clinical data from our and published UPD patients with those with deletions we observed the following: the age of diagnosis is higher in UPD group (average 7 3 ⁄12 years), microcephaly is more frequent among deletion patients, UPD children start walking earlier (average age 2 9 ⁄12 years), whereas in deletion patients the average is 4 1 ⁄2 years, epilepsy started later in UPD patients (average 5 10 ⁄12 years) than in deletion patients (average 1 11 ⁄12 years), weight above the 75th centile is reported mainly in UPD patients, complete absence of speech is more common in the deleted (88.9%) than in the UPD patients because half of the children are able to say few words. Thus, besides the abnormalities already described, the UPD patients have somewhat better verbal development, a weight above the 75th centile, and OFC in the upper normal range. Am. J. Med. Genet. 92:322-327, 2000.
Epilepsy Research, 2005
The authors describe the electroclinical phenotype of four patients with Angelman syndrome (AS) determined by its rarest genetic mechanism-uniparental disomy (UPD). The analysis of ours and published patients showed that in UPD, when epilepsy occurred, it was milder compared to patients with deletion, although a suggestive EEG was observed in most patients. We found that UPD patients do not completely fit the scenario delineated for AS, suggesting that patients determined by different mechanisms should be distinctly addressed, for a better understanding of this syndrome.
Phenotypic variability in Angelman syndrome - report of two cases
2008
Angelman syndrome is a genetic condition, characterized by severe mental retardation, ataxic gait, severe speech delay, dysmorphic features, abnormal behaviours, movement disorder. It is caused by a variety of genetic mechanisms which all interfere with expression of the UBE3A gene on chromosome 15q11-13. In this paper, we present two cases of Angelman syndrome, one of them with classical phenotype, and the other with a Rett syndrome – like phenotype. In both patients, the molecular cytogenetic investigation confirmed the interstitial deletion within critical region 15q11-13.
Cytogenetic and molecular analysis in Angelman syndrome
American Journal of Medical Genetics, 1993
We report on cytogenetic and molecular analyses of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG-and GBG-banded chromosomes were studied. Standard molecular analysis with six 15qllq13 DNA sequences was used to analyze copy number and parental origin of 15qllq13. Concordance between molecular and cytogenetic data was excellent. The combined data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15qllq13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone to de novo deletion.
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