A de novo duplication of Xp11.22-p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome
A de novo duplication of Xp11.22-p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome
Only a small number of individuals with duplications within the proximal short arm of the X chromosome have been reported. The majority of patients have duplications encompassing Xp11-p21, or extend more distally into Xp22. We report on a female patient who presented within the first year of life with plagiocephaly, speech delay, and epilepsy. Brain MRI showed a relatively thin cerebral cortex, abnormal periventricular white matter, and abnormal vessels in the left inferior parietal region. Cytogenetic and microsatellite analysis of the patient and her parents showed that she has a de novo duplication of Xp11.22-Xp11.4 on her paternal X chromosome. FISH analysis using fluorescently labeled BACs followed by array analysis including an X tilepath BAC array showed that a 12.3 Mb interval between 40.4 Mb and 52.7 Mb from the Xp telomere (NCBI build 36) was duplicated and excluded the presence of additional rearrangements along the X chromosome. Interestingly, X-inactivation studies in peripheral blood leukocytes showed that the duplicated (paternal) X chromosome was active in the majority of cells, in contrast to other patients with Xp duplications in whom X inactivation is random or skewed toward the normal X. These findings suggest that overexpression of genes from proximal Xp is likely to have contributed to her clinical phenotype.
xp duplication, x chromosome structural anomaly, xp11.2, x chromosome inactivation
1735-1740
Holden, Simon T.
8a5e6552-637a-4730-ba55-8ea50053d369
Clarkson, Amanda
f718ee76-04b4-4c7d-94ab-53468ff943d4
Thomas, N. Simon
1a601957-288d-4f12-a9f7-4f4279b7f9b3
Abbott, Kristin
ff2eec6d-ec56-4fa3-a1f4-fd1649348917
James, Matthew R.
26591d0e-0d33-4ae9-8d7b-91ad62cf4be5
Willatt, Lionel
8bcb2c89-bb9b-46c9-a354-f395986cbd69
4 June 2010
Holden, Simon T.
8a5e6552-637a-4730-ba55-8ea50053d369
Clarkson, Amanda
f718ee76-04b4-4c7d-94ab-53468ff943d4
Thomas, N. Simon
1a601957-288d-4f12-a9f7-4f4279b7f9b3
Abbott, Kristin
ff2eec6d-ec56-4fa3-a1f4-fd1649348917
James, Matthew R.
26591d0e-0d33-4ae9-8d7b-91ad62cf4be5
Willatt, Lionel
8bcb2c89-bb9b-46c9-a354-f395986cbd69
Holden, Simon T., Clarkson, Amanda, Thomas, N. Simon, Abbott, Kristin, James, Matthew R. and Willatt, Lionel
(2010)
A de novo duplication of Xp11.22-p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome.
American Journal of Medical Genetics part A, 152A (7), .
(doi:10.1002/ajmg.a.33457).
Abstract
Only a small number of individuals with duplications within the proximal short arm of the X chromosome have been reported. The majority of patients have duplications encompassing Xp11-p21, or extend more distally into Xp22. We report on a female patient who presented within the first year of life with plagiocephaly, speech delay, and epilepsy. Brain MRI showed a relatively thin cerebral cortex, abnormal periventricular white matter, and abnormal vessels in the left inferior parietal region. Cytogenetic and microsatellite analysis of the patient and her parents showed that she has a de novo duplication of Xp11.22-Xp11.4 on her paternal X chromosome. FISH analysis using fluorescently labeled BACs followed by array analysis including an X tilepath BAC array showed that a 12.3 Mb interval between 40.4 Mb and 52.7 Mb from the Xp telomere (NCBI build 36) was duplicated and excluded the presence of additional rearrangements along the X chromosome. Interestingly, X-inactivation studies in peripheral blood leukocytes showed that the duplicated (paternal) X chromosome was active in the majority of cells, in contrast to other patients with Xp duplications in whom X inactivation is random or skewed toward the normal X. These findings suggest that overexpression of genes from proximal Xp is likely to have contributed to her clinical phenotype.
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Published date: 4 June 2010
Keywords:
xp duplication, x chromosome structural anomaly, xp11.2, x chromosome inactivation
Organisations:
Human Genetics
Identifiers
Local EPrints ID: 159337
URI: http://eprints.soton.ac.uk/id/eprint/159337
ISSN: 0148-7299
PURE UUID: db163693-e2bc-4811-bd14-0e9d29f81c5e
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Date deposited: 29 Jun 2010 13:53
Last modified: 14 Mar 2024 01:53
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Contributors
Author:
Simon T. Holden
Author:
Amanda Clarkson
Author:
N. Simon Thomas
Author:
Kristin Abbott
Author:
Matthew R. James
Author:
Lionel Willatt
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