Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1-q14.2.

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Publication year
2009Source
European Journal of Human Genetics, 17, 8, (2009), pp. 1024-1033ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Journal title
European Journal of Human Genetics
Volume
vol. 17
Issue
iss. 8
Page start
p. 1024
Page end
p. 1033
Subject
DCN 2: Functional Neurogenomics; IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of diseaseAbstract
Split hand-split foot malformation or ectrodactyly is a heterogeneous congenital defect of digit formation. The aim of this study is the mapping of the breakpoints and a detailed molecular characterization of the candidate genes for an isolated and syndromic form of ectrodactyly, both associated with de novo apparently balanced chromosome translocations involving the same chromosome 2 band, [t(2;11)(q14.2;q14.2)] and [t(2;4)(q14.1;q35)], respectively. Breakpoints were mapped by fluorescence in situ hybridization using bacterial artificial chromosome clones. Where possible, these breakpoints were further delimited. Candidate genes were screened for pathogenic mutations and the expression levels of two of them analysed. The isolated bilateral split foot malformation-associated chromosome 2 breakpoint was localized at 120.9 Mb, between the two main candidate genes, encoding GLI-Kruppel family member GLI2 and inhibin-betaB. The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1. No clear pathogenic mutations were identified in any of these genes. The breakpoint between INHBB and GLI2 coincides with a previously identified translocation breakpoint associated with ectrodactyly. We propose a mechanism by which translocations in the 2q14.1-q14.2 region disrupt the specific arrangement of long-range regulatory elements that control the tight quantitative spatiotemporal expression of one or more genes from the breakpoint region.
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- Academic publications [204968]
- Electronic publications [103219]
- Faculty of Medical Sciences [81049]
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