Neonatal Dubin-Johnson syndrome: long-term follow-up and MRP2 mutations study.
Neonatal Dubin-Johnson syndrome (DJS) is rarely diagnosed and mutational analysis of multidrug-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.
Lee
Jyh-Hong
JH
Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
Chen
Huey-Ling
HL
Chen
Hui-Ling
HL
Ni
Yen-Hsuan
YH
Hsu
Hong-Yuan
HY
Chang
Mei-Hwei
MH
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007566:Jaundice, Chronic Idiopathic / Q000235:genetics* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human