The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders
The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders
This study investigated the phenotypic manifestations of interstitial duplications of chromosome 15 that involve the Prader-Willi/Angelman syndrome critical region (PWACR). Twenty-one affected individuals from six families were evaluated in detail, using standardized and semi-standardized measures of intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as well as the relationship between the parental origin of the duplication and the phenotypic effects. Assessments of the affected individuals were compared with evaluations of the unaffected relatives from the same families. Results indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. Three of these cases were probands and only one met criteria for classic autism. There was very little evidence of the duplication cosegregating with autism spectrum disorder diagnosis. Paternally inherited duplications were significantly less likely to give rise to phenotypic effects. The findings indicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotypic expression is dependent on the parental origin of the duplication and implicate maternally active genes in the pathogenesis of the developmental impairments. Further research will be required to clarify the range and basis of the phenotypic manifestations.
autism, chromosome 15, duplication, pwacr, imprinting, 15q11-q13
675-685
Bolton, Patrick Farrar
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Dennis, N.R.
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Browne, C.E.
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Thomas, N.S.
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Veltman, M.W.M.
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Thompson, R.J.
49ef1427-c727-4426-8d1b-6b32e84fa20d
Jacobs, P.
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8 December 2001
Bolton, Patrick Farrar
3a76d737-de81-4b4f-8558-90c9db92bddb
Dennis, N.R.
154aa617-52e2-4711-98ef-89fef8610de7
Browne, C.E.
3ba0ce5a-74c7-4564-a274-334c7a39c221
Thomas, N.S.
df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4
Veltman, M.W.M.
4e141e97-e709-48a8-b7aa-ed5316a3075c
Thompson, R.J.
49ef1427-c727-4426-8d1b-6b32e84fa20d
Jacobs, P.
44a49fb2-53e9-428e-a20c-373b75e457f1
Bolton, Patrick Farrar, Dennis, N.R., Browne, C.E., Thomas, N.S., Veltman, M.W.M., Thompson, R.J. and Jacobs, P.
(2001)
The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders.
American Journal of Medical Genetics part A, 105 (8), .
(doi:10.1002/ajmg.1551).
Abstract
This study investigated the phenotypic manifestations of interstitial duplications of chromosome 15 that involve the Prader-Willi/Angelman syndrome critical region (PWACR). Twenty-one affected individuals from six families were evaluated in detail, using standardized and semi-standardized measures of intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as well as the relationship between the parental origin of the duplication and the phenotypic effects. Assessments of the affected individuals were compared with evaluations of the unaffected relatives from the same families. Results indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. Three of these cases were probands and only one met criteria for classic autism. There was very little evidence of the duplication cosegregating with autism spectrum disorder diagnosis. Paternally inherited duplications were significantly less likely to give rise to phenotypic effects. The findings indicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotypic expression is dependent on the parental origin of the duplication and implicate maternally active genes in the pathogenesis of the developmental impairments. Further research will be required to clarify the range and basis of the phenotypic manifestations.
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Published date: 8 December 2001
Keywords:
autism, chromosome 15, duplication, pwacr, imprinting, 15q11-q13
Organisations:
Human Genetics
Identifiers
Local EPrints ID: 24631
URI: http://eprints.soton.ac.uk/id/eprint/24631
ISSN: 0148-7299
PURE UUID: eef5d0d2-1a2b-4999-a2c3-115f11fa2619
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Date deposited: 04 Apr 2006
Last modified: 15 Mar 2024 06:57
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Contributors
Author:
Patrick Farrar Bolton
Author:
N.R. Dennis
Author:
C.E. Browne
Author:
N.S. Thomas
Author:
M.W.M. Veltman
Author:
R.J. Thompson
Author:
P. Jacobs
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