Inside the 8p23.1 duplication syndrome; eight microduplications of likely or uncertain clinical significance

2.50
Hdl Handle:
http://hdl.handle.net/11287/594017
Title:
Inside the 8p23.1 duplication syndrome; eight microduplications of likely or uncertain clinical significance
Authors:
Barber, J. C.; Rosenfeld, J. A.; Graham, J. M.; Kramer, N.; Lachlan, K. L.; Bateman, M. S.; Collinson, M. N.; Stadheim, B. F.; Turner, Claire L.; Gauthier, J. N.; Reimschisel, T. E.; Qureshi, A. M.; Dabir, T. A.; Humphreys, M. W.; Marble, M.; Huang, T.; Beal, S. J.; Massiah, J.; Taylor, E. J.; Wynn, S. L.
Abstract:
The 8p23.1 duplication syndrome (8p23.1 DS) is a recurrent genomic condition with an estimated prevalence of 1 in 58,000. The core 3.68 Mb duplication contains 32 genes of which five are currently candidates for the phenotypic features. Here we describe four patients and five families with eight microduplications of 8p23.1 ranging from 187 to 1082 kb in size and one atypical duplication of 4 Mb. These indicate that a minimal region of overlap (MRO) in medial 8p23.1 can give rise to features of 8p23.1 DS including developmental delay, dysmorphism, macrocephaly and otitis media, but not congenital heart disease (CHD). This MRO spans 776 kb (chr8:10,167,881-10,943,836 hg19) and contains SOX7 and seven of the other 32 core 8p23.1 DS genes. In centromeric 8p23.1, microduplications including GATA4 can give rise to non-syndromic CHD but the clinical significance of two smaller centromeric microduplications without GATA4 was uncertain due to severe neurological profiles not usually found in 8p23.1 DS. The clinical significance of three further 8p23.1 microduplications was uncertain due to additional genetic factors without which the probands might not have come to medical attention. Variable expressivity was indicated by the almost entirely unaffected parents in all five families and the mildly affected sibling in one. Intronic interruptions of six genes by microduplication breakpoint intervals had no apparent additional clinical consequences. Our results suggest that 8p23.1 DS is an oligogenetic condition largely caused by the duplication and interactions of the SOX7 and GATA4 transcription factors.
Citation:
Am J Med Genet A. 2015 Sep;167A(9):2052-64.
Publisher:
Wiley
Journal:
American journal of medical genetics. Part A
Issue Date:
11-Jun-2015
URI:
http://hdl.handle.net/11287/594017
DOI:
10.1002/ajmg.a.37120
PubMed ID:
26097203
Additional Links:
http://dx.doi.org/10.1002/ajmg.a.37120
Type:
Journal Article
Language:
eng
ISSN:
1552-4833
Appears in Collections:
2015 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorBarber, J. C.en
dc.contributor.authorRosenfeld, J. A.en
dc.contributor.authorGraham, J. M.en
dc.contributor.authorKramer, N.en
dc.contributor.authorLachlan, K. L.en
dc.contributor.authorBateman, M. S.en
dc.contributor.authorCollinson, M. N.en
dc.contributor.authorStadheim, B. F.en
dc.contributor.authorTurner, Claire L.en
dc.contributor.authorGauthier, J. N.en
dc.contributor.authorReimschisel, T. E.en
dc.contributor.authorQureshi, A. M.en
dc.contributor.authorDabir, T. A.en
dc.contributor.authorHumphreys, M. W.en
dc.contributor.authorMarble, M.en
dc.contributor.authorHuang, T.en
dc.contributor.authorBeal, S. J.en
dc.contributor.authorMassiah, J.en
dc.contributor.authorTaylor, E. J.en
dc.contributor.authorWynn, S. L.en
dc.date.accessioned2016-01-19T12:38:38Zen
dc.date.available2016-01-19T12:38:38Zen
dc.date.issued2015-06-11en
dc.identifier.citationAm J Med Genet A. 2015 Sep;167A(9):2052-64.en
dc.identifier.issn1552-4833en
dc.identifier.pmid26097203en
dc.identifier.doi10.1002/ajmg.a.37120en
dc.identifier.urihttp://hdl.handle.net/11287/594017en
dc.description.abstractThe 8p23.1 duplication syndrome (8p23.1 DS) is a recurrent genomic condition with an estimated prevalence of 1 in 58,000. The core 3.68 Mb duplication contains 32 genes of which five are currently candidates for the phenotypic features. Here we describe four patients and five families with eight microduplications of 8p23.1 ranging from 187 to 1082 kb in size and one atypical duplication of 4 Mb. These indicate that a minimal region of overlap (MRO) in medial 8p23.1 can give rise to features of 8p23.1 DS including developmental delay, dysmorphism, macrocephaly and otitis media, but not congenital heart disease (CHD). This MRO spans 776 kb (chr8:10,167,881-10,943,836 hg19) and contains SOX7 and seven of the other 32 core 8p23.1 DS genes. In centromeric 8p23.1, microduplications including GATA4 can give rise to non-syndromic CHD but the clinical significance of two smaller centromeric microduplications without GATA4 was uncertain due to severe neurological profiles not usually found in 8p23.1 DS. The clinical significance of three further 8p23.1 microduplications was uncertain due to additional genetic factors without which the probands might not have come to medical attention. Variable expressivity was indicated by the almost entirely unaffected parents in all five families and the mildly affected sibling in one. Intronic interruptions of six genes by microduplication breakpoint intervals had no apparent additional clinical consequences. Our results suggest that 8p23.1 DS is an oligogenetic condition largely caused by the duplication and interactions of the SOX7 and GATA4 transcription factors.en
dc.language.isoengen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1002/ajmg.a.37120en
dc.titleInside the 8p23.1 duplication syndrome; eight microduplications of likely or uncertain clinical significanceen
dc.typeJournal Articleen
dc.identifier.journalAmerican journal of medical genetics. Part Aen

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