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8p23.1 duplication syndrome; a novel genomic condition with unexpected complexity revealed by array CGH4

8p23.1 duplication syndrome; a novel genomic condition with unexpected complexity revealed by array CGH4
8p23.1 duplication syndrome; a novel genomic condition with unexpected complexity revealed by array CGH4
The 8p23.1 deletion syndrome is established but not an equivalent duplication syndrome. Here, we report five patients; a de novo prenatal case and two families in which 8p23.1 duplications have been directly transmitted from mothers to children. Dual-colour fluorescent in situ hybridisation, multiplex ligation-dependent probe amplification analysis and customised oligonucleotide array comparative genomic hybridisation (oaCGH) indicated an approximately 3.75 Mb duplication of most of band 8p23.1 between the olfactory receptor/defensin repeats (ORDRs) in all cases. However, oaCGH revealed an additional duplication of 500 kb adjacent to the proximal ORDR in Family 1 and an additional deletion of 3.14 Mb within the Nablus Mask-Like Facial Syndrome region of 8q22.1 in Family 2. Copy number variation at introns 4-5 of the GATA4 gene was also identified. This 8p23.1 duplication syndrome is associated with a characteristic facial phenotype including a prominent forehead and arched eyebrows. Adrenal insufficiency, Tetralogy of Fallot, partial 2/3 syndactyly of the toes and cleft palate in some individuals may be explained by ascertainment bias, incomplete penetrance and/or the presence of the microdeletion in Family 2. The duplication is compatible with normal early childhood development but, although our adult cases live independent lives with varying degrees of support, learning difficulties have been experienced by some family members. We conclude that the 8p23.1 duplication syndrome is a genomic condition with an emerging but variable phenotype that may be under-diagnosed. Our results demonstrate that direct transmission does not distinguish genuine duplications from euchromatic variants and illustrate the power of array CGH to reveal unexpected additional imbalances in affected patients.
nucleic acid hybridization, multiple, childhood, fluorescence, pair 8, report, family, chromosome aberrations, adrenal insufficiency, newborn, introns, research support, chromosomes, laboratories, patients, abnormalities, cytogenetics, infant, analysis, human, genetics, female, male, research, tetralogy of fallot, adult, syndrome, gene dosage, mothers, pregnancy, molecular biology, phenotype, humans, toes, transmission, oligonucleotide array sequence analysis, in situ hybridization
1018-4813
18-27
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Maloney, V.K.
02588a50-e8b2-486b-8d54-53cb32a0a035
Huang, S.
a8beb2a3-8e04-4d81-b6b8-453af8791721
Bunyan, D.J.
41347b93-e79b-4026-93f9-dd1004cfa05e
Cresswell, L.
7e300d97-8aef-4d49-8421-0b8b6b3b338c
Kinning, E.
f44f67d2-8635-4a63-86a6-27009896ed54
Benson, A.
f133a021-5618-4801-bd21-c5cfe078e735
Cheetham, T.
cd036e45-2052-4a02-9a34-0ba4d9d81e89
Wyllie, J.
dfa10f89-82ea-4e67-a96d-737e78253b9e
Lynch, S.A.
e0ef4dce-34aa-4399-ade1-cac605ce9ca6
Zwolinski, S.
7f1912dd-3885-4470-b517-2b79011646c1
Prescott, L.
0dd80740-1a06-4f96-85a8-0bdd59ebed22
Crow, Y.
60599f78-39e1-4ce0-a5e4-fcdd225dacd4
Morgan, R.
595c9900-8c30-48ca-a853-bf44b2a876f3
Hobson, E.
d9bc0869-847f-404c-9bc3-53580eb38fe4
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Maloney, V.K.
02588a50-e8b2-486b-8d54-53cb32a0a035
Huang, S.
a8beb2a3-8e04-4d81-b6b8-453af8791721
Bunyan, D.J.
41347b93-e79b-4026-93f9-dd1004cfa05e
Cresswell, L.
7e300d97-8aef-4d49-8421-0b8b6b3b338c
Kinning, E.
f44f67d2-8635-4a63-86a6-27009896ed54
Benson, A.
f133a021-5618-4801-bd21-c5cfe078e735
Cheetham, T.
cd036e45-2052-4a02-9a34-0ba4d9d81e89
Wyllie, J.
dfa10f89-82ea-4e67-a96d-737e78253b9e
Lynch, S.A.
e0ef4dce-34aa-4399-ade1-cac605ce9ca6
Zwolinski, S.
7f1912dd-3885-4470-b517-2b79011646c1
Prescott, L.
0dd80740-1a06-4f96-85a8-0bdd59ebed22
Crow, Y.
60599f78-39e1-4ce0-a5e4-fcdd225dacd4
Morgan, R.
595c9900-8c30-48ca-a853-bf44b2a876f3
Hobson, E.
d9bc0869-847f-404c-9bc3-53580eb38fe4

Barber, J.C., Maloney, V.K., Huang, S., Bunyan, D.J., Cresswell, L., Kinning, E., Benson, A., Cheetham, T., Wyllie, J., Lynch, S.A., Zwolinski, S., Prescott, L., Crow, Y., Morgan, R. and Hobson, E. (2008) 8p23.1 duplication syndrome; a novel genomic condition with unexpected complexity revealed by array CGH4. European Journal of Human Genetics, 16 (1), 18-27. (doi:10.1038/sj.ejhg.5201932).

Record type: Article

Abstract

The 8p23.1 deletion syndrome is established but not an equivalent duplication syndrome. Here, we report five patients; a de novo prenatal case and two families in which 8p23.1 duplications have been directly transmitted from mothers to children. Dual-colour fluorescent in situ hybridisation, multiplex ligation-dependent probe amplification analysis and customised oligonucleotide array comparative genomic hybridisation (oaCGH) indicated an approximately 3.75 Mb duplication of most of band 8p23.1 between the olfactory receptor/defensin repeats (ORDRs) in all cases. However, oaCGH revealed an additional duplication of 500 kb adjacent to the proximal ORDR in Family 1 and an additional deletion of 3.14 Mb within the Nablus Mask-Like Facial Syndrome region of 8q22.1 in Family 2. Copy number variation at introns 4-5 of the GATA4 gene was also identified. This 8p23.1 duplication syndrome is associated with a characteristic facial phenotype including a prominent forehead and arched eyebrows. Adrenal insufficiency, Tetralogy of Fallot, partial 2/3 syndactyly of the toes and cleft palate in some individuals may be explained by ascertainment bias, incomplete penetrance and/or the presence of the microdeletion in Family 2. The duplication is compatible with normal early childhood development but, although our adult cases live independent lives with varying degrees of support, learning difficulties have been experienced by some family members. We conclude that the 8p23.1 duplication syndrome is a genomic condition with an emerging but variable phenotype that may be under-diagnosed. Our results demonstrate that direct transmission does not distinguish genuine duplications from euchromatic variants and illustrate the power of array CGH to reveal unexpected additional imbalances in affected patients.

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More information

Published date: 2008
Keywords: nucleic acid hybridization, multiple, childhood, fluorescence, pair 8, report, family, chromosome aberrations, adrenal insufficiency, newborn, introns, research support, chromosomes, laboratories, patients, abnormalities, cytogenetics, infant, analysis, human, genetics, female, male, research, tetralogy of fallot, adult, syndrome, gene dosage, mothers, pregnancy, molecular biology, phenotype, humans, toes, transmission, oligonucleotide array sequence analysis, in situ hybridization

Identifiers

Local EPrints ID: 59484
URI: https://eprints.soton.ac.uk/id/eprint/59484
ISSN: 1018-4813
PURE UUID: 360db1c6-8ae4-412a-8606-7ce810b14fb1

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Date deposited: 03 Sep 2008
Last modified: 13 Mar 2019 20:30

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Contributors

Author: J.C. Barber
Author: V.K. Maloney
Author: S. Huang
Author: D.J. Bunyan
Author: L. Cresswell
Author: E. Kinning
Author: A. Benson
Author: T. Cheetham
Author: J. Wyllie
Author: S.A. Lynch
Author: S. Zwolinski
Author: L. Prescott
Author: Y. Crow
Author: R. Morgan
Author: E. Hobson

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