Sun Hao-Zhe, Shi Hong, Zhang Shun-Cai, Shen Xi-Zhong
Hao-Zhe Sun, Hong Shi, Shun-Cai Zhang, Xi-Zhong Shen, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
World J Gastroenterol. 2015 Jan 14;21(2):699-703. doi: 10.3748/wjg.v21.i2.699.
Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3 (PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T (p.L59L) mutation in exon 4, c.504C>T (p.N168N) mutation in exon 6, c.711A>T (p.I237I) mutation in exon 8, c.874A>T (p.K292X) in exon 9 and a novel mutation, c.1804G>T (p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602W in exon 15 was predicted as probably damaging by PolyPhen-2 with a score of 0.986 (sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.
基因分型对于3型进行性家族性肝内胆汁淤积症（PFIC3）的诊断具有决定性意义。在此，我们报告1例ABCB4基因存在复合突变的中国PFIC3患者。对1例病因不明的肝内胆汁淤积症17岁男性患者进行了肝活检。肝脏组织学检查结果提示肝内胆汁淤积伴广泛纤维化。基因分型显示，第4外显子存在c.175C>T（p.L59L）突变，第6外显子存在c.504C>T（p.N168N）突变，第8外显子存在c.711A>T（p.I237I）突变，第9外显子存在c.874A>T（p.K292X）突变，以及1个新突变，第15外显子存在c.1804G>T（p.G602W）突变。基于这些发现，该患者被诊断为PFIC3。第15外显子的新突变p.G602W经PolyPhen-2预测可能具有损害性，得分0.986（敏感性：0.54；特异性：0.94），经SIFT评分预测会影响蛋白质功能，评分为0.01。
