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Citations
... During the last 2 years we were able to investigate additional 15 patients from 15 families. Thus, 65 unrelated JBS-affected families (by November 2016) were studied at our institution, of which a majority of 59 families has already been published by Sukalo (2016). The study was approved by the Ethics Board of the Medical Faculty of the University of Erlangen. ...
Background
Johanson‐Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N‐end rule pathway.
Methods
Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease‐causing UBR1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation‐dependent probe amplification (MLPA) analysis of the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons.
Results
Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease‐associated UBR1 alleles. Six patients with a highly suggestive clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA analysis detected six alleles harboring exon deletions/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127/130 alleles).
Conclusion
We conclude that single or multi‐exon deletions or duplications account for a substantial proportion of JBS‐associated UBR1 mutations.
