Separation of the PROX1 gene from upstream conserved elements in a complex inversion/translocation patient with hypoplastic left heart. Export

@article{citeulike:4670051, abstract = {Hypoplastic left heart (HLH) occurs in at least 1 in 10 000 live births but may be more common in utero. Its causes are poorly understood but a number of affected cases are associated with chromosomal abnormalities. We set out to localize the breakpoints in a patient with sporadic HLH and a de novo translocation. Initial studies showed that the apparently simple 1q41;3q27.1 translocation was actually combined with a 4-Mb inversion, also de novo, of material within 1q41. We therefore localized all four breakpoints and found that no known transcription units were disrupted. However we present a case, based on functional considerations, synteny and position of highly conserved non-coding sequence elements, and the heterozygous Prox1(+/-) mouse phenotype (ventricular hypoplasia), for the involvement of dysregulation of the PROX1 gene in the aetiology of HLH in this case. Accordingly, we show that the spatial expression pattern of PROX1 in the developing human heart is consistent with a role in cardiac development. We suggest that dysregulation of PROX1 gene expression due to separation from its conserved upstream elements is likely to have caused the heart defects observed in this patient, and that PROX1 should be considered as a potential candidate gene for other cases of HLH. The relevance of another breakpoint separating the cardiac gene ESRRG from a conserved downstream element is also discussed.European Journal of Human Genetics advance online publication, 27 May 2009; doi:10.1038/ejhg.2009.91.}, author = {Gill, Harinder K. K. and Parsons, Sian R. R. and Spalluto, Cosma and Davies, Angela F. F. and Knorz, Victoria J. J. and Clare and Bee and Carter, Nigel P. P. and Caroline and Wilson, David I. I. and Roberts, Roland G. G.}, citeulike-article-id = {4670051}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ejhg.2009.91}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19471316}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19471316}, day = {27}, doi = {10.1038/ejhg.2009.91}, issn = {1476-5438}, journal = {European journal of human genetics : EJHG}, keywords = {disease}, month = {May}, posted-at = {2009-05-28 21:50:35}, priority = {2}, title = {Separation of the PROX1 gene from upstream conserved elements in a complex inversion/translocation patient with hypoplastic left heart.}, url = {http://dx.doi.org/10.1038/ejhg.2009.91}, year = {2009} }

TY - JOUR ID - citeulike:4670051 L3 - citeulike-article-id:4670051 N2 - Hypoplastic left heart (HLH) occurs in at least 1 in 10 000 live births but may be more common in utero. Its causes are poorly understood but a number of affected cases are associated with chromosomal abnormalities. We set out to localize the breakpoints in a patient with sporadic HLH and a de novo translocation. Initial studies showed that the apparently simple 1q41;3q27.1 translocation was actually combined with a 4-Mb inversion, also de novo, of material within 1q41. We therefore localized all four breakpoints and found that no known transcription units were disrupted. However we present a case, based on functional considerations, synteny and position of highly conserved non-coding sequence elements, and the heterozygous Prox1(+/-) mouse phenotype (ventricular hypoplasia), for the involvement of dysregulation of the PROX1 gene in the aetiology of HLH in this case. Accordingly, we show that the spatial expression pattern of PROX1 in the developing human heart is consistent with a role in cardiac development. We suggest that dysregulation of PROX1 gene expression due to separation from its conserved upstream elements is likely to have caused the heart defects observed in this patient, and that PROX1 should be considered as a potential candidate gene for other cases of HLH. The relevance of another breakpoint separating the cardiac gene ESRRG from a conserved downstream element is also discussed.European Journal of Human Genetics advance online publication, 27 May 2009; doi:10.1038/ejhg.2009.91. JF - European journal of human genetics : EJHG SN - 1476-5438 TI - Separation of the PROX1 gene from upstream conserved elements in a complex inversion/translocation patient with hypoplastic left heart. KW - disease AU - Gill, Harinder AU - Parsons, Sian AU - Spalluto, Cosma AU - Davies, Angela AU - Knorz, Victoria AU - Clare AU - Bee AU - Carter, Nigel AU - Caroline AU - Wilson, David AU - Roberts, Roland PY - 2009/05/27/ UR - http://dx.doi.org/10.1038/ejhg.2009.91 ER -