ABSTRACT
Johanson-Blizzard syndrome (JBS) is a rare genetic disorder caused by Ubiquitin Protein Ligase E3 Component N-Recognin1 (UBR1) gene mutations. It is characterized by exocrine pancreatic insufficiency, craniofacial deformities, sensorineural hearing loss, and a broad variety of intellectual disabilities. The aim of our study is to report four pediatric cases (three of which are siblings, and the fourth patient is unrelated) that presented some features of JBS. The cases have been confirmed by genetic testing to have mutations in the UBR1 gene. This case series study was conducted retrospectively, giving a detailed description of the demographic and clinical information of these four cases, and reflecting our experience with this subset of patients. All these cases have been treated at the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, and were identified by their clinical and laboratory markers that favor JBS. A novel homozygous missense mutation c.2075 T > C (p. lle692Thr) in exon 18 (UBR1: NM_174916.3) was identified and confirmed by Sanger sequencing in all our cases outlined in this paper. These presented cases illustrate the phenotypic variability and complexity of JBS and the importance of physical examination to reach a diagnosis. The identified novel mutation in this study broadens the spectrum of UBR1 mutations that contribute to JBS.
