Clinical manifestation of Johanson-Blizzard syndrome in patient with nucleotide variants in UBR1 gene

Introduction. Johanson-Blizzard syndrome is a very rare genetic disorder caused by a mutation of the ubiquitin protein ligase E3 component N-recognin 1 (UBR1). Clinical diagnosis is based on the pathognomonic combination of congenital exocrine pancreatic insufficiency with facial dysmorphology (nasal wing hypo/aplasia, and oligodontia of permanent teeth). Diagnosis is confirmed by genetic screening of the UBR1 gene. The purpose of this case report is to emphasize that nucleotide variants in the UBR1 gene that are described as benign or unclassified should be considered as genetic causes in patients with clinical characteristics of Johanson-Blizzard syndrome. Case report. In this report, we present an 8-month old child who was admitted to our hospital due to poor weight gain and loose stools. On admission, the signs of protein-energy malnutrition, with facial dysmorphological signs and other anomalies, were observed. He had hypotonia and convergent strabismus. A laboratory examination confirmed exocrine pancreatic insufficiency and hypothyroidism. Genetic testing confirmed two single nucleotide variants in ubiquitin protein ligase E3 component N-Recognin 1, chromosome 15q15.2: NM_174916.3:c.4700+12A>G (intron 42), and NM_174916.3 UBR1:c.862-18C>T (intron 07). A pancreatic enzyme replacement therapy with liposoluble vitamin supplementation and adequate nutrition was conducted. Conclusion. Recognition of clinical features of Johanson-Blizzard syndrome and genetic confirmation is very important, especially in patients with idiopathic pancreatic insufficiency. Even when genetic confirmation is not possible, adequate treatment is necessary for normal growth and development of the child.