Neonatal Dubin-Johnson syndrome: Long-term follow-up and MRP2 mutations study
Journal
Pediatric Research
Journal Volume
59
Journal Issue
4 PART 1
Pages
584-589
Date Issued
2006
Author(s)
Abstract
Neonatal Dubin-Johnson syndrome (DJS) is rarely diagnosed and mutational analysis of multidrag-resistance-associated protein 2 (MRP2) in such patients had not been reported. We aimed to investigate the possible correlations between genotype and phenotype of patients with DJS. Four cases of DJS, two diagnosed during the neonatal period and two diagnosed at adolescence, were followed for 5-20 y. Mutational analysis in the MRP2/ABCC2 gene was performed in all four cases. Biphasic pattern of jaundice attack was observed in one patient who was followed for 20 y, with jaundice subsiding before 1 y of age and recurring at adolescence. Six novel mutations in four patients were found, including deletions (2748del136, 3615del229, and Del3399-3400), and missense mutations (L441M and E1352Q) and nonsense mutation (Y1275X). The immunohistochemical staining in liver tissues from two patients with neonatal onset showed negative staining for MRP2. Reviewing previously reported cases, all patients diagnosed as DJS before 10 y of age have mutations involving one of the two ATP-binding cassettes (ABC) of the MRP2. This study suggests that long-term follow-up is indicated for neonatal DJS because of possible recurrence and/or second attacks of jaundice in later life, and that disruption of functionally important ABC domains in MRP2 may be related to the earlier onset of the disease. Copyright ? 2006 International Pediatric Research Foundation, Inc.
SDGs
Other Subjects
ABC transporter; bilirubin; multidrug resistance protein 2; adolescent; article; bilirubin blood level; case report; clinical feature; correlation analysis; Dubin Johnson syndrome; follow up; gene; gene deletion; genotype phenotype correlation; human; human tissue; immunohistochemistry; liver biopsy; male; missense mutation; mrp2 gene; mutational analysis; newborn; newborn jaundice; nonsense mutation; phototherapy; priority journal; protein domain; recurrent disease; symptom; Adolescent; Adult; Child; Child, Preschool; DNA Mutational Analysis; Follow-Up Studies; Genotype; Humans; Infant; Infant, Newborn; Jaundice, Chronic Idiopathic; Liver; Male; Membrane Transport Proteins; Middle Aged; Multidrug Resistance-Associated Proteins; Mutation; Phenotype
Type
journal article