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Eur J Hum Genet. 2011 May;19(5):540-6. doi: 10.1038/ejhg.2010.245. Epub 2011 Feb 2.

Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development.

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1
McDermott Center for Human Growth and Development and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

Erratum in

  • Eur J Hum Genet. 2012 Feb;20(2):249. Garg, Vidu [added].

Abstract

We studied a man with distal hypospadias, partial anomalous pulmonary venous return, mild limb-length inequality and a balanced translocation involving chromosomes 9 and 13. To gain insight into the etiology of his birth defects, we mapped the translocation breakpoints by high-resolution comparative genomic hybridization (CGH), using chromosome 9- and 13-specific tiling arrays to analyze genetic material from a spontaneously aborted fetus with unbalanced segregation of the translocation. The chromosome 13 breakpoint was ∼400  kb away from the nearest gene, but the chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2), a gene that encodes an evolutionarily conserved nuclear zinc-finger protein. The BNC2/Bnc2 gene is abundantly expressed in developing mouse and human periurethral tissues. In all, 6 of 48 unrelated subjects with distal hypospadias had nine novel nonsynonymous substitutions in BNC2, five of which were computationally predicted to be deleterious. In comparison, two of 23 controls with normal penile urethra morphology, each had a novel nonsynonymous substitution in BNC2, one of which was predicted to be deleterious. Bnc2(-/-) mice of both sexes displayed a high frequency of distal urethral defects; heterozygotes showed similar defects with reduced penetrance. The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development.

PMID:
21368915
PMCID:
PMC3083624
DOI:
10.1038/ejhg.2010.245
[Indexed for MEDLINE]
Free PMC Article
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