Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause. (12th September 2013)

• Record Type: Journal Article
• Authors: 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.; Holder‐Espinasse, M.
• Is Part Of: Clinical genetics. Volume 86:Number 3(2014:Sep.)
• Page Start: 246
• Page End: 251
• Publication Date: 2013-09-12
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12259
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12259-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12259-para-0001">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 <italic>SF3B4</italic> gene as the cause of this condition in most patients. <italic>SF3B4</italic> encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed <italic>SF3B4</italic> sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss‐of‐function. <italic>SF3B4</italic> 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.</p> </abstract>