Identification and expression analysis of a novel intragenic EFNB1 mutation causing craniofrontonasal syndrome

•A novel EFNB1 truncating mutation in craniofrontonasal syndrome (CFNS) is reported.•Expression analyses suggest that nonsense-mediated RNA decay acts on this mutation.•Our report expands the EFNB1 mutational and functional spectrum in CFNS.

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by mutations in the EFNB1 gene and characterized by distinctive craniofacial and digital malformations. In contrast with most X-linked traits, female patients with CFNS display a more severe phenotype than males. In this report, the clinical, molecular and RNA expression analyses of a female subject with CFNS are described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated in this patient. To assess the effect of this novel mutation at the transcript level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our knowledge, this is the first time that an EFNB1 transcript carrying a truncating mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated mRNA decay. Our results expand the mutational spectrum of CFNS and add to the functional consequences of truncating EFNB1 mutations.