The authors declare no conflict of interest.
Article first published online: 13 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 2, pages 333–339, February 2012
How to Cite
Lopez, E., Callier, P., Cormier-Daire, V., Lacombe, D., Moncla, A., Bottani, A., Lambert, S., Goldenberg, A., Doray, B., Odent, S., Sanlaville, D., Gueneau, L., Duplomb, L., Huet, F., Aral, B., Thauvin-Robinet, C. and Faivre, L. (2012), Search for a gene responsible for Floating-Harbor syndrome on chromosome 12q15q21.1. Am. J. Med. Genet., 158A: 333–339. doi: 10.1002/ajmg.a.34401
How to Cite this Article: Lopez E, Callier P, Cormier-Daire V, Lacombe D, Moncla A, Bottani A, Lambert S, Goldenberg A, Doray B, Odent S, Sanlaville D, Gueneau L, Duplomb L, Huet F, Aral B, Thauvin-Robinet C, Faivre. L. 2012. Search for a gene responsible for Floating-Harbor syndrome on chromosome 12q15q21.1. Am J Med Genet Part A 158A:333–339.
- Issue published online: 19 JAN 2012
- Article first published online: 13 JAN 2012
- Manuscript Accepted: 19 OCT 2011
- Manuscript Received: 21 APR 2011
- GIS-Institut des Maladies Rares
- Dijon University Hospital and the General Counsil of Burgundy. Grant Number: AOI 2009
- Floating Harbor syndrome;
- 12q15q21.1 microdeletion, high-throughput sequencing
Floating-Harbor syndrome (FHS) is characterized by characteristic facial dysmorphism, short stature with delayed bone age, and expressive language delay. To date, the gene(s) responsible for FHS is (are) unknown and the diagnosis is only made on the basis of the clinical phenotype. The majority of cases appeared to be sporadic but rare cases following autosomal dominant inheritance have been reported. We identified a 4.7 Mb de novo 12q15-q21.1 microdeletion in a patient with FHS and intellectual deficiency. Pangenomic 244K array-CGH performed in a series of 12 patients with FHS failed to identify overlapping deletions. We hypothesized that FHS is caused by haploinsufficiency of one of the 19 genes or predictions located in the deletion found in our index patient. Since none of them appeared to be good candidate gene by their function, a high-throughput sequencing approach of the region of interest was used in eight FHS patients. No pathogenic mutation was found in these patients. This approach failed to identify the gene responsible for FHS, and this can be explained by at least four reasons: (i) our index patient could be a phenocopy of FHS; (ii) the disease may be clinically heterogeneous (since the diagnosis relies exclusively on clinical features), (iii) these could be genetic heterogeneity of the disease, (iv) the patient could carry a mutation in a gene located elsewhere. Recent descriptions of patients with 12q15-q21.1 microdeletions argue in favor of the phenocopy hypothesis. © 2012 Wiley Periodicals, Inc.