Please Support our AS
Research in
Australia
Donations to:
Research Account – this is held at the
Children’s Hospital at Westmead, Locked Bag
4001, Westmead NSW 2145 Australia. Donations
made to this account are tax deductible and
you will get a receipt. Cheques must be made
payable to – The Children’s Hospital at
Westmead. This is necessary for the fund
raising department’s accounting system and
for you to claim it as a tax.deduction.
Please accompany the cheque with a covering
letter, with your name and address, stating
that the money is specifically for the
Angelman Syndrome Research Account, or Dr.
Ellie Smith in Cytogenetics. Please state
the account no. 691904.
Past Research
In the past in Australia, collaboration with
the genetics laboratory at the University of
Sydney, headed by Professor Ron Trent, has
identified several families with UBE3A
mutation, milder phenotype for patients with
UPD and various new DNA markers.
See below for some of the grants obtained
and Australian publications we have had.
Future Research
There are several possibilities for AS
research in Australia – for example an AS
Database.
There is currently no collective information
available on AS in Australia – neither the
frequency, age at diagnosis, family studies
or common complications in our patients.
So, a really worthy project would be to set
up and maintain a data base of all patients.
This would provide several answers to
frequently asked questions, one of which is
"how many people with AS are there in Oz?"
With follow up information recorded,
it would provide a valuable resource for the
natural history of AS in our society – what
level of achievement is reached, surgical
interventions required, improvement or
otherwise of epilepsy, living accommodation
and medical problems which could arise, life
span, to name a few. A most interesting
question is – are there any symptoms which
occur with age which are not yet described
or known – i.e. rare manifestations?
Routine UBE3A gene Testing for Certain Patients.
Chromosome 15(q11-13) is a complex genetic
region, involving imprinting.
AS arises from either a deletion (70%), UPD
(5%), an imprinting centre (IC) defect (5%)
or a mutation (change) in the UBE3A gene for
AS (10%), other epigenetic mechanism in 10%.
The deletion, UPD and IC defect can be
readily ascertained: the 10% with possible
UBE3A mutation require additional testing.
UBE3A Testing
in Australia
For the first time in Australia, testing for
the UBE3A gene sequencing is now available
through the Mater Health Services Pathology
in Brisbane, Queensland. This is a
fee-for-service testing. Please refer to
your Geneticist / Paediatrician to order
this test.
Information for
Paediatricians/Geneticists/Laboratories:
Queries regarding the UBE3A gene sequencing
can be directed the following contacts at
the Department of Pathology, Mater Health
Services Brisbane:
Dr David M. Cowley FRCPA, FHGSA,
Director of Chemical Pathology
David.Cowley@mater.org.au
Mr Ivan McGown MHGSA,
Supervising Scientist, Molecular Genetic
Ivan.McGown@mater.org.au
Telephone: 07 3163 8500
Australian Research Achievements & Grants
1995-6 Australian - European Awards Program
- 2 year - for "DNA Methylation Testing in
Angelman Syndrome", with Dr. Tina Buchholz,
Germany.
1992 – 1996 NHMRC - 5 years - with Professor
R Trent "Molecular Studies in the
Prader-Willi and
Angelman Syndrome".
1991- 2 Clive and Vera Ramaciotti
Foundations grant - with Prof. R Trent
"Development of the in-situ hybridisation
technique to study the PWS and AS”.
Publications
*Smith A, Deng Z-M, Beran R,
Woodage T, Trent RJ. Familial unbalanced
translocation t(8;15)(p23.3;q11) with
uniparental disomy in Angelman Syndrome. Hum
Genet 1994; 93:471-3 *Woodage T, Lindeman R,
Deng Z-M, Fimmel A, Smith A, Trent RJ.
Physical mapping studies at D15S10:
implications for candidate gene
identification in the Angelman syndrome/PWS
chromosome region of 15q11-13. Genomics
1994; 19:170-172.
*Smith A. Angelman Syndrome: Genetic
mechanisms and relationship to Prader-Willi
syndrome. ANZJ Devel. Dis 1994; 19: 259 -
267.
*Jauch A, Robson L, Smith A. Investigations
with fluorescence in situ hybridisation
(FISH) demonstrate loss of the telomeres on
the reciprocal chromosome in three
unbalanced translocations involving
chromosome 15 in Prader-Willi and Angelman
syndrome. Hum Genet 1995; 96: 345-349.
*Smith A, Deng Z-M, Prasad M, Robson L,
Woodage T, Trent R. Comparison of high
resolution cytogenetics, fluorescence in
situ hybridisation (FISH) and DNA studies to
validate the diagnosis of Prader-Willi &
Angelman syndromes.Arch Dis Child 1995;72:
397-402.
*Buchholz T, Schuffenhauer S, Evans K,
Robson L, Appleton B, Smith A. Molecular
analysis of an extra inv dup (15)(q13)
chromosome in two patients with Angelman
syndrome. Acta Genetica Medica et Gemellol
1996; 45:217-220.
*Leitner RP, Smith A. An Angelman syndrome
clinic: report on 24 patients seen in the
first year. J Ped Child Health 1996; 32:
94-98.
Smith A, Marks R, Haan E, Dixon J, Trent RJ.
Clinical features in 4 patients with
Angelman syndrome resulting from paternal
uniparental disomy. J Med Genet
1997;34:426-429.
*Sandanam T, Beange H, Robson L, Woolnough
H, Buchholz T, Smith A. Manifestations in
institutionalised adults with Angelman
syndrome due to DNA deletion. Am J Med Genet
1997;70:415-20
*Buchholz T, Smith E. Genomic Imprinting:
DNA methylation test available for patients.
Todays Life Science 1997; 9: 36-39.
*Buchholz T, Jackson J, Smith A. Methylation
analysis at three different loci within the
imprinted region of chromosome 15q11-13. Am
J Med Genet 1997; 72:117-120 Letter.
*Trent RJ, Sheffield LJ, Deng Z-M, Kim WS,
Nassif NT, Ryce C, Woods CG, Michaelis RC,
Tarleton J, Smith A. The elusive Angelman
syndrome critical region. J Med Genet 1997;
34: 714-718.
*Smith A, Robson L, Buchholz T. Diagnostic
testing for Prader-Willi (PWS) and Angelman
(AS) syndromes: Response. Am J Hum Genet
1997; 61:241-44. Letter.
*Smith A, Robson L, Buchholz T. Angelman
syndrome due to paternal UPD: two more cases
with normal growth. Clin Genet 1998;
53:223-225.
*Ellaway C, Buchholz T, Smith A, Leonard H,
Christodoulou J. Rett syndrome: significant
clinical overlap with Angelman syndrome but
not with methylation status. J Child Neurol
1998;13:448-451.
*Fung DCY, Yu B, Cheong KF, Smith A, Trent
RJ. UBE3A “mutations” in two unrelated and
phenotypically different Angelman syndrome
patients. Hum Genet 1998; 102:487-92
*Buiting K, Dittrich B, Gross S, Lich C,
Farber C, Buchholz T, Smith E, Reis A,
Burger J, Nothen M, Barthwitte U, Janssen B,
Abeliovich D, Lerner I, Schrander-Stumpel C,
Smeets H, Meinecke P, Malcolm S, Gardner A,
Lalande M, Nicholls R, Tommerup N, Matthijs
G, Kokkonen H, Hilbert P, van Maldergem L,
Glover G, Carbonell P, Willems P,
Gillessen-Kaesbach G, Horsthemke B. Sporadic
imprinting defects in Prader-Willi syndrome
and Angelman syndrome:implications for
imprint switching, genetic counselling and
prenatal diagnosis. Am J Hum Genet 1998 ;
63: 170-180.
*Runte M, Farber C, Lich C, Zeschnigk M,
Buchholz T, Smith A, van Maldergem L, Burger
J, Muscatelli F, Gilleson- Kaesbach G,
Horsthemke B, Buiting K. Comprehensive
methylation analysis in typical and atypical
PWS and AS patients with normal biparental
chromosomes 15. Eur J Hum Genet 2001;
9:519-526.
*Smith A, Robson L, St. Heaps L. Use of two
FISH probes provides a cost- effective,
simple protocol to exclude an imprinting
centre defect in routine laboratory testing
for suspected Prader-Willi and Angelman
syndrome. Ann Genet 2002: 45;189-191.
Prepared by Ellie Smith, Professional
Consultant and Patron, Angelman Syndrome
Association, Australia and Angelman New
Zealand. 30.3.09.
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