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8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families

BACKGROUND: The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our...

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Autores principales: Barber, John CK, Bunyan, Dave, Curtis, Merryl, Robinson, Denise, Morlot, Susanne, Dermitzel, Anette, Liehr, Thomas, Alves, Claudia, Trindade, Joana, Paramos, Ana I, Cooper, Clare, Ocraft, Kevin, Taylor, Emma-Jane, Maloney, Viv K
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846957/
https://www.ncbi.nlm.nih.gov/pubmed/20167067
http://dx.doi.org/10.1186/1755-8166-3-3
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author Barber, John CK
Bunyan, Dave
Curtis, Merryl
Robinson, Denise
Morlot, Susanne
Dermitzel, Anette
Liehr, Thomas
Alves, Claudia
Trindade, Joana
Paramos, Ana I
Cooper, Clare
Ocraft, Kevin
Taylor, Emma-Jane
Maloney, Viv K
author_facet Barber, John CK
Bunyan, Dave
Curtis, Merryl
Robinson, Denise
Morlot, Susanne
Dermitzel, Anette
Liehr, Thomas
Alves, Claudia
Trindade, Joana
Paramos, Ana I
Cooper, Clare
Ocraft, Kevin
Taylor, Emma-Jane
Maloney, Viv K
author_sort Barber, John CK
collection PubMed
description BACKGROUND: The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis. METHODS: Additional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH). RESULTS: Three cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome. CONCLUSIONS: Our data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity.
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spelling pubmed-28469572010-03-30 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families Barber, John CK Bunyan, Dave Curtis, Merryl Robinson, Denise Morlot, Susanne Dermitzel, Anette Liehr, Thomas Alves, Claudia Trindade, Joana Paramos, Ana I Cooper, Clare Ocraft, Kevin Taylor, Emma-Jane Maloney, Viv K Mol Cytogenet Research BACKGROUND: The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis. METHODS: Additional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH). RESULTS: Three cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome. CONCLUSIONS: Our data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity. BioMed Central 2010-02-18 /pmc/articles/PMC2846957/ /pubmed/20167067 http://dx.doi.org/10.1186/1755-8166-3-3 Text en Copyright ©2010 Barber et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Barber, John CK
Bunyan, Dave
Curtis, Merryl
Robinson, Denise
Morlot, Susanne
Dermitzel, Anette
Liehr, Thomas
Alves, Claudia
Trindade, Joana
Paramos, Ana I
Cooper, Clare
Ocraft, Kevin
Taylor, Emma-Jane
Maloney, Viv K
8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title_full 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title_fullStr 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title_full_unstemmed 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title_short 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
title_sort 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846957/
https://www.ncbi.nlm.nih.gov/pubmed/20167067
http://dx.doi.org/10.1186/1755-8166-3-3
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