Expanding the mutational spectrum in Johanson-Blizzard syndrome: identification of whole exon deletions and duplications in the UBR1 gene by multiplex ligation-dependent probe amplification analysis.
Severe presentation of JBS usually involves deleterious (nonsense, frameshift, or splice-site) mutations in the UBR1 gene that are thought to completely abolish the expression of a functional protein product, as in this familial case; however, milder presentation of JBS has occasionally been observed with missense mutations in at least 1 of the 2 copies of UBR1, in which there may be residual activity of the product of this gene.
Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS.
Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS.
Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients.
Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients.
Molecular studies revealed a novel homozygous nonsense mutation in exon 38 of the UBR1 gene, which confirmed the diagnosis of Johanson-Blizzard syndrome.
We report on two apparently unrelated girls with Johanson-Blizzard syndrome (JBS), in both children caused by a homozygous IVS26+5G>A mutation in the UBR1 gene.
We report the case of a 7-year-old female with pancreatic insufficiency and mild phenotypic features, in whom the diagnosis of JBS was established using recently described molecular testing for the UBR1 gene.