The authors declare no conflict of interest.
Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause
Article first published online: 12 SEP 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 86, Issue 3, pages 246–251, September 2014
How to Cite
Petit, F., Escande, F., Jourdain, A.S., Porchet, N., Amiel, J., Doray, B., Delrue, M.A., Flori, E., Kim, C.A., Marlin, S., Robertson, S.P., Manouvrier-Hanu, S. and Holder-Espinasse, M. (2014), Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause. Clinical Genetics, 86: 246–251. doi: 10.1111/cge.12259
- Issue published online: 20 AUG 2014
- Article first published online: 12 SEP 2013
- Accepted manuscript online: 4 SEP 2013 11:59AM EST
- Manuscript Accepted: 19 AUG 2013
- Manuscript Revised: 16 JUL 2013
- Manuscript Received: 4 JUN 2013
- acro-facial dysostosis;
- Nager syndrome;
Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss-of-function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype–phenotype correlations. Most mutation-negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity.