Recurrent Johanson-Blizzard syndrome in a triplet pregnancy complicated by urethral obstruction sequence: a clinical, molecular, and immunohistochemical approach.

Abstract

We report on a triplet pregnancy of consanguineous parents with one fetus being affected by recurrent Johanson-Blizzard syndrome (JBS). At autopsy in the 35th gestational week, the affected triplet presented with an especially severe and lethal manifestation of the disorder as compared to his elder affected brother and to cases in the literature, thus exemplifying great interfamilial and intrafamilial phenotypic variability. Arhinencephaly and cystic renal dysplasia associated with urethral obstruction sequence were features not described previously in the literature. In addition to the lack of exocrine acini as the characteristic feature of JBS, the pancreas revealed a resorptive inflammatory reaction with infiltration by eosinophilic granulocytes that focally dispersed onto islets of Langerhans, thus favoring a progressive destructive rather than primary dysplastic process and possibly explaining the occurrence of diabetes mellitus in later life. JBS maps to chromosome 15q15-q21.1 and is associated with mutations in the UBR1 gene. Testing the fetus and the affected sibling revealed a homozygous truncating mutation in UBR1. The resulting absence of the UBR1 protein was confirmed by Western blot. Immunohistochemical staining using a commercial anti-UBR1 antibody demonstrated staining, presumably artifactual. This finding suggests that, until an appropriately validated antibody has been identified, this modality should not be utilized for diagnosis or confirmation of this disorder.

• Authors: Katharina Schoner, Barbara Fritz, Georg Huelskamp, Frank Louwen, Martin Zenker, Roland Moll, Helga Rehder
• Journal: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society (Pediatr Dev Pathol) Vol. 15 Issue 1 Pg. 50-7 ( 2012) ISSN: 1093-5266 [Print] United States
• PMID: 21711208 (Publication Type: Case Reports, Journal Article)

Chemical References

• UBR1 protein, human
• Ubiquitin-Protein Ligases

Topics

• Adult
• Anus, Imperforate
• Child, Preschool
• Consanguinity
• Constriction, Pathologic (genetics, metabolism, pathology)
• Deafness (genetics, metabolism, pathology)
• Ectodermal Dysplasia (genetics, metabolism, pathology)
• Fatal Outcome
• Female
• Fetal Death
• Gestational Age
• Growth Disorders
• Hearing Loss, Sensorineural
• Humans
• Hydronephrosis (genetics, metabolism, pathology)
• Hypothyroidism (genetics, metabolism, pathology)
• Intellectual Disability
• Male
• Mutation
• Nasal Mucosa (metabolism)
• Nose (abnormalities, pathology)
• Oligohydramnios (genetics, metabolism, pathology)
• Pancreas (pathology)
• Pancreatic Diseases (genetics, metabolism, pathology)
• Pancreatitis
• Peripheral Vascular Diseases (genetics, metabolism, pathology)
• Pregnancy
• Pregnancy, Triplet
• Prune Belly Syndrome (genetics, metabolism, pathology)
• Recurrence
• Ubiquitin-Protein Ligases (deficiency, genetics)
• Urethral Obstruction (genetics, metabolism, pathology)