Jiao Jingjing, Morotti Raffaella, Shafizadeh Nafis, Jain Dhanpat
Department of Pathology, Yale School of Medicine, New Haven, CT, US.
Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, Los Angeles, CA, US.
Am J Clin Pathol. 2025 Mar 8;163(3):332-339. doi: 10.1093/ajcp/aqae123.
Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis.
The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed.
Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES.
These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.
进行性家族性肝内胆汁淤积症（PFIC）是一组常染色体隐性疾病，由胆汁分泌或运输缺陷引起，通常在儿童期表现为胆汁淤积。在此，我们描述3例具有诊断挑战的PFIC病例，并强调基因分析的作用。
回顾了每个病例的临床病史、实验室数据、肝活检和分子分析。
病例1是一名来自波多黎各的西班牙裔男性，自2个月大起出现肝肿大，17岁时通过全外显子组测序（WES）在ATP结合盒亚家族B成员4（ABCB4）中鉴定出纯合剪接位点变异（c.2784-12T>C）后，最终被诊断为PFIC3。病例2是一名37岁男性，有酗酒史、肝功能检查异常和活检显示胆管减少。分子检测发现致病性杂合ABCB4突变（c.1633C>T）变异，导致诊断为PFIC3。病例3是一名2岁女性，最初表现为药物性肝损伤，但通过WES在肌球蛋白VB（MYO5B）中鉴定出杂合移码突变（p.Asp300Trpfs*19）和杂合错义突变（c.1357T>C）后，被诊断为PFIC10。
这些PFIC病例突出了其临床表现的异质性和诊断挑战，并强调了下一代测序的作用，特别是WES的实用性。
