Sangkhathat Surasak, Laochareonsuk Wison, Maneechay Wanwisa, Kayasut Kanita, Chiengkriwate Piyawan
Pediatric Surgery Unit, Department of Surgery, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Central Research Laboratory, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
J Pediatr Genet. 2018 Jun;7(2):67-73. doi: 10.1055/s-0038-1632395. Epub 2018 Feb 16.
Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction-direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in (Alagille syndrome), 2 in (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in (Dubin-Johnson syndrome), (PFIC type 2), (Crigler-Najjar syndrome), (Kabuki syndrome), (Mitchell-Riley syndrome), (Fanconi anemia), and (Zimmermann-Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.
胆道闭锁（BA）是婴儿期发生的最严重的梗阻性胆管病形式。BA的明确诊断通常依赖于手术所见以及肝外胆管中发现的支持性病理模式。在婴儿期，胆汁淤积的重叠临床模式可见于其他疾病，包括胆管发育不全和进行性家族性肝内胆汁淤积。此外，BA在一些罕见的遗传综合征中被报道为一种表型。与BA不同，其他胆管病表型有其各自已确定的遗传标记。在本研究中，我们使用这些标记在诊断为BA的病例中寻找其他胆汁淤积实体。通过手术所见和组织病理学诊断为BA的20例病例的DNA，使用全外显子测序对19个与婴儿胆汁淤积综合征相关的基因进行研究。变异选择集中在dbSNP150中等位基因频率小于0.01的那些变异。所有选定的变异通过聚合酶链反应直接测序进行验证。在研究的20例病例中，在9个基因中检测到13个罕见变异：4个在（阿拉吉耶综合征），2个在（进行性家族性肝内胆汁淤积[PFIC]6型），以及各1个在（杜宾-约翰逊综合征）、（PFIC2型）、（克里格勒-纳贾尔综合征）、（歌舞伎综合征）、（米切尔-莱利综合征）、（范可尼贫血）和（齐默尔曼-拉班德综合征）。在诊断为BA的病例中检测到与各种胆汁淤积综合征相关的基因病变，这提出了一个假设，即BA中的严重炎症性胆管病可能不是一种独特的疾病实体，而是几种婴儿胆汁淤积综合征之间的共同病理。
