Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. 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. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

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Introduction: COVID-19 has a less severe course in children. In April 2020, some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU). This study aimed to describe the prevalence and clinical characteristics of KD SARS-CoV-2 confirmed and negative patients during the pandemic in Spain.Material and Methods: Medical data of KD patients from January 1, 2018 until May 30, 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (March 1–May 30, 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV–) to those from the same period during 2018 and 2019 (PreCoV).Results: One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004, respectively). CoV+ patients were significantly older (7.5 vs. 2.5 yr) and mainly non-Caucasian (64 vs. 29%), had incomplete KD presentation (73 vs. 32%), lower leucocyte (9.5 vs. 15.5 × 109) and platelet count (174 vs. 423 × 109/L), higher inflammatory markers (C-Reactive Protein 18.5vs. 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4,766 vs. 505 pg/ml), less aneurysm development (3.8 vs. 11.1%), and more myocardial dysfunction (30.8 vs. 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period.Conclusion: The KD CoV+ patients mostly meet pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multisystem inflammatory syndrome in children criteria. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.

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