Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
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DOI：
10.1016/j.aohep.2021.100342
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发表时间：
2021-04-08
影响因子：
3.8
通讯作者：
Jankowska, Irena
中科院分区：
文献类型：
--
作者：
Lipinski, Patryk;Ciara, Elzbieta;Jankowska, Irena
导言和目标：进行性家族性肝内胆汁淤积3型（PFIC-3）是一种罕见的常染色体隐性遗传胆汁淤积性肝病，由ABCB 4基因突变引起。本研究的目的是介绍在一个转诊中心诊断的4名波兰PFIC-3患者的表型和基因型谱。材料与方法：该研究包括4例胆汁淤积和ABCB 4基因致病性变异的患者，这些变异是通过靶基因组的下一代测序（NGS）或全外显子组测序（WES）鉴定的。收集临床、实验室、组织学和分子数据。结果：确定了4名患者（3名男性）。首次出现临床体征和症状的年龄分别为6岁、2.5岁、14岁和2岁;平均年龄为6岁。这些体征和症状包括瘙痒（4例患者中的2例）和肝肿大伴脾肿大（4例患者中的4例）。转诊到我们中心时的年龄分别为9岁、3岁、15岁和2.5岁，而平均年龄为7岁。病因不明的慢性胆汁淤积性肝病在他们所有人都成立。在末次随访访视时对所有患者进行NGS分析。包括c.902T>A，p.Met301Lys，c.3279+1G>A，p.？，3524T>A、p.Leu1175His。从第一次咨询到最终诊断的时间分别为14年、9年、3年和1年，平均为6.8年。提供了详细的后续行动。结论：PFIC-3的临床表型可能是可变的。PFIC-3的临床和生化诊断困难，因此NGS研究在做出正确诊断方面非常有用。(c)2021年丰达西翁临床医学，A.C.由Elsevier Espana出版，S.L.U.这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Introduction and objectives: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed in a one-referral centre. Materials and methods: The study included 4 patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing (NGS) of a targeted-gene panel or whole exome sequencing (WES). Clinical, laboratory, histological, and molecular data were collected. Results: Four patients (three males) were identified. The age at first noted clinical signs and symptoms was 6, 2.5, 14, and 2 years respectively; the mean age was 6 years. Those signs and symptoms include pruritus (2 out of 4 patients) and hepatomegaly with splenomegaly (4 out of 4 patients). The age at the time of referral to our centre was 9, 3, 15, and 2.5 years respectively, while the mean age was 7 years. Chronic cholestatic liver disease of unknown aetiology was established in all of them. The NGS analysis was performed in all patients at the last follow-up visit. Three novel variants including c.902T>A, p.Met301Lys, c.3279+1G>A, p.?, and c.3524T>A, p.Leu1175His were identified. The time from the first consultation to the final diagnosis was 14, 9, 3, and 1 year respectively; the mean was 6.8 years. A detailed follow-up was presented. Conclusions: The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis. (c) 2021 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).