Communicated by Stylianos E. Antonarakis
Mutation Spectrum and Genotype–Phenotype Correlation in Cornelia de Lange Syndrome
Article first published online: 16 SEP 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 12, pages 1589–1596, December 2013
How to Cite
Mannini, L., Cucco, F., Quarantotti, V., Krantz, I. D. and Musio, A. (2013), Mutation Spectrum and Genotype–Phenotype Correlation in Cornelia de Lange Syndrome. Hum. Mutat., 34: 1589–1596. doi: 10.1002/humu.22430
Contract grant sponsors: Region of Tuscany (AM), NIH/NICHD PO1 HD 052860 (IDK) and the Center for Cornelia de Lange Syndrome and Related Diagnoses at the Children's Hospital of Philadelphia (IDK).
- Issue published online: 13 NOV 2013
- Article first published online: 16 SEP 2013
- Accepted manuscript online: 29 AUG 2013 09:40AM EST
- Manuscript Accepted: 20 AUG 2013
- Manuscript Received: 11 JUN 2013
- Region of Tuscany (AM). Grant Number: NIH/NICHD PO1 HD 052860
- Center for Cornelia de Lange Syndrome and Related Diagnoses at the Children's Hospital of Philadelphia (IDK)
- Cornelia de Lange syndrome;
Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. Clinical features include growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. The increased understanding of the genetic basis of CdLS has led to diagnostic improvement and expansion of the phenotype. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. Approximately 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. To date, 311 CdLS-causing mutations are known including missense, nonsense, small deletions and insertions, splice site mutations, and genomic rearrangements. Phenotypic variability is seen both intra- and intergenically. This article reviews the spectrum of CdLS mutations with a particular emphasis on their correlation to the clinical phenotype.