Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause.

Abstract

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.

• Authors: F Petit, F Escande, A S Jourdain, N Porchet, J Amiel, B Doray, M A Delrue, E Flori, C A Kim, S Marlin, S P Robertson, S Manouvrier-Hanu, M Holder-Espinasse
• Journal: Clinical genetics (Clin Genet) Vol. 86 Issue 3 Pg. 246-51 (Sep 2014) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 24003905 (Publication Type: Journal Article)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• RNA-Binding Proteins
• SF3B4 protein, human

Topics

• Base Sequence
• Female
• Genes, Dominant (genetics)
• Genetic Predisposition to Disease (genetics)
• Haploinsufficiency (genetics)
• Humans
• Male
• Mandibulofacial Dysostosis (genetics, pathology)
• Molecular Sequence Data
• Mutation (genetics)
• Phenotype
• RNA-Binding Proteins (genetics)
• Sequence Analysis, DNA