User talk:Z3291643
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1721745/pdf/v089p0F436.pdf--Sang Lee 21:32, 17 August 2011 (EST)
Identify a review and a research article related to your group topic.
This research article showed genotype-phenotype correlations in Angelman Syndrome (AS). They have concluded that deletion patients had worse developmental outcomes than non deletion patients. Abstract at PMID 20729760
This review article is really comprehensive and gives a good background knowledge of AS. Astract at PMID 20445456
--z3291643 21:37, 10 August 2011 (EST)
Timeline
| Year | Notes |
|---|---|
| 1965 | First reported by Dr Harry Angelman- Initially called this disorder “Happy Puppet Syndrome” |
| 1980s | First reports of AS reaches US and research into the disorder being at the University of Florisa under the direction of Dr. Charles Williams. |
| 1987 | Discovery of a genetic marker for AS – an absent genetic code on chromosome 15 |
| 1997 | The cause of AS discovered by Dr. Joseph Wagstaff and Dr. Arthur Beaudet – mutation or deletion in the UBE3A gene. |
| Current | Four different genetic abnormalities for AS confirmed by genetic testing; Deletion, Uniparental Disomy (UPD), Imprinting and UBE3A mutation. |
--Sang Lee 23:22, 1 September 2011 (EST)
Aetiology
Chromosome 15 became associated with AS in the 1980s after the observation of many AS patients harboring microdeletions of 15q11.2-15q13. [1] The last decade has shed even more light in the aetiology of AS,as Kishino and Matsuura first identified UBE3A as the causative gene for AS in 1997. [2] [3] Although the function of UBE3A is known (encodes for a ubiuitin ligase enzyme),its function in the development of the nervous system and the process of UBE3A mutation leading to cognitive impairment in AS patients is still vague. [4]
Different genetic mechanisms lead to different clinical phenotypes of AS. The most common genetic mechanism leading to AS is the deletion or re-arrangement of maternal chromosome at locus 15q11.2-q13, accounting 60-75% of AS occurrences. This leads to more severe clinical phenotypes of microcephaly, motor difficulties, seizures and impaired speech development. The next most common genetic mechanism is mutation in the UBE3A gene responsible for 10% of AS cases and paternal uniparental disomy and mutation in the imprinting centre (IC), both accounting 2-5% of AS observed.
AS is caused by the 4 major genetic mechanisms mentioned above and are thus divided into Classes I to IV based on their underlying genetic mechanism. AS patients with the clinical features of AS but no cytogenetic or molecular abnormality in Chromosome 15q11.2-13 are grouped under Class V (summarised in table below).
| Class | Mechanism | Diagnostic Tests | Frequency |
| Ia | De novo deletion | High resolution cytogenetics FISH | 60-75% |
| Ib | Deletion due to chromosome rearrangement | High resolution cytogenetics FISH | <1% |
| II | Paternal uniparental disomy | RFLP analysis | 2% |
| IIIa | Imprinting defect with IC mutation | Screening of IC for mutations is positive | 2% |
| IIIb | Imprinting defect withouth IC mutation | Screening of IC for mutations is negative | 2% |
| IIIc | Mosaic imprinting defect | Screening of IC for mutations is usually negative | ? |
| IV | UBE3A mutation | Screening of UBE3A for mutations | 5-10% |
| V | No identifiable genetic abnormality | Consider other diagnoses | 5-26% |
| Adapted from Smith JC, et al. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003;40:87-95 | |||
