Delineation of a 2.2 Mb microdeletion at 5q35 associated with microcephaly and congenital heart disease
Version of Record online: 6 FEB 2006
Copyright © 2006 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 140A, Issue 5, pages 427–433, 1 March 2006
How to Cite
Bækvad-Hansen, M., Tümer, Z., Delicado, A., Erdogan, F., Tommerup, N. and Larsen, L. A. (2006), Delineation of a 2.2 Mb microdeletion at 5q35 associated with microcephaly and congenital heart disease. Am. J. Med. Genet., 140A: 427–433. doi: 10.1002/ajmg.a.31087
- Issue online: 13 FEB 2006
- Version of Record online: 6 FEB 2006
- Manuscript Accepted: 17 OCT 2005
- Manuscript Received: 28 APR 2005
- The Danish Heart Association
- Ronald McDonald House Charities
- congenital heart disease;
Fine mapping of chromosomal deletions and genotype–phenotype comparisons of clinically well-defined patients can be used to confirm or reveal loci and genes associated with human disorders. Eleven patients with cytogenetically visible deletions involving the terminal region of chromosome 5q have been described, but the extent of the deletion was determined only in one case. In this study we describe a 15-year-old boy with Ebstein anomaly, atrial septal defect (ASD), atrioventricular (AV) conduction defect, and microcephaly. He had an apparently balanced paracentric inversion of chromosome 5, with the karyotype 46, XY,inv(5)(q13q35) de novo. Further mapping of the chromosome breakpoints using fluorescence in situ hybridization (FISH) revealed a 2.2 Mb microdeletion at the 5q35 breakpoint, which spans 16 genes, including the cardiac homeobox transcription factor gene NKX2-5. The current data suggest that haploinsufficiency of NKX2-5 cause Ebstein anomaly and support previous results showing that NKX2-5 mutations cause ASD and AV conduction defect. Furthermore, we suggest presence of a new microcephaly locus within a 2.2 Mb region at 5q35.1–q35.2. © 2006 Wiley-Liss, Inc.