Carlton V E, Knisely A S, Freimer N B
Department of Biochemistry and Biophysics, University of California, San Francisco, USA.
Hum Mol Genet. 1995 Jun;4(6):1049-53. doi: 10.1093/hmg/4.6.1049.
A locus for progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, has been mapped to a 19 cM region of chromosome 18 by a search for shared segments, using patients from the Amish kindred in which the disorder was originally described. A similar liver disease, benign recurrent intrahepatic cholestasis (BRIC), recently has been mapped to the same region, suggesting that these two diseases are caused by mutations in the same gene. Although PFIC and BRIC are clinically distinct diseases, episodic attacks of jaundice and pruritus, with elevated concentrations of bile acid in serum, are seen in both disorders. In PFIC patients, these attacks result in progressive liver damage and death. The clinical and biochemical features of PFIC and BRIC are suggestive of a defect in primary bile acid secretion. The biology of bile secretion is of great interest because of its vital importance in digestion of dietary fats as well as in secretion of xenobiotics and metabolic waste products. Cloning of the gene (or genes) responsible for PFIC and BRIC will likely provide important insights into this pathway.
一种进行性家族性肝内胆汁淤积症（PFIC），也称为比勒病，通过寻找共享片段，利用最初描述该疾病的阿米什家族的患者，已被定位到18号染色体上一个19厘摩的区域。一种类似的肝病，良性复发性肝内胆汁淤积症（BRIC），最近也被定位到同一区域，这表明这两种疾病是由同一基因的突变引起的。尽管PFIC和BRIC在临床上是不同的疾病，但两种疾病都出现黄疸和瘙痒的发作，同时血清胆汁酸浓度升高。在PFIC患者中，这些发作会导致进行性肝损伤和死亡。PFIC和BRIC的临床和生化特征提示原发性胆汁酸分泌存在缺陷。胆汁分泌生物学因其在膳食脂肪消化以及外源性物质和代谢废物分泌中的至关重要性而备受关注。克隆负责PFIC和BRIC的基因可能会为这条途径提供重要见解。
