Neonatal Dubin-Johnson Syndrome: Long-term follow-up and MRP2 mutations study
Neonatal Dubin-Johnson Syndrome: Long-term follow-up and MRP2 mutations study
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DOI：
10.1203/01.pdr.0000203093.10908.bb
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Chang, MH
中科院分区：
文献类型：
--
作者：
Lee, JH;Chen, HL;Chang, MH
新生儿杜宾-约翰逊综合征（DJS）很少被诊断出来，并且尚未报道此类患者的多药耐药相关蛋白2（MRP 2）突变分析。我们的目的是研究DJS患者的基因型和表型之间可能存在的相关性。4例DJS，2例在新生儿期诊断，2例在青春期诊断，随访5-20年。在所有4例病例中进行了MRP 2/ABCC 2基因突变分析。1例随访20年，黄疸呈双相型，1岁前消退，青春期复发。在4例患者中发现了6个新的突变，包括缺失（2748 de 1136、3615 del 229和De 13399 -3400）、错义突变（L441 M和E1352 Q）和无义突变（Y1275 X）。2例新生儿发病患者肝组织免疫组化染色显示MRP 2阴性。回顾以前报道的病例，所有在10岁之前诊断为DJS的患者都有涉及MRP 2的两个ATP结合盒（ABC）之一的突变。这项研究表明，长期随访是指新生儿DJS，因为可能复发和/或黄疸在以后的生活中的第二次攻击，并在MRP 2的功能重要的ABC域的破坏可能与早期发病的疾病。
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 I y of age and recurring at adolescence. Six novel mutations in four patients were found, including deletions (2748de1136, 3615del229, and De13399-3400), 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.