Familial hypercholanemia (FHC) is characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. We show here that FHC in Amish individuals is associated with mutations in tight junction protein 2 (encoded by TJP2, also known as ZO-2) and bile acid Coenzyme A: amino acid N-acyltransferase (encoded by BAAT). The mutation of TJP2, which occurs in the first PDZ domain, reduces domain stability and ligand binding in vitro. We noted a morphological change in hepatic tight junctions. The mutation of BAAT, a bile acid-conjugating enzyme, abrogates enzyme activity; serum of individuals homozygous with respect to this mutation contains only unconjugated bile acids. Mutations in both TJP2 and BAAT may disrupt bile acid transport and circulation. Inheritance seems to be oligogenic, with genotype at BAAT modifying penetrance in individuals homozygous with respect to the mutation in TJP2.

中文翻译：

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家族遗传性高胆固醇血症的复杂遗传以及TJP2和BAAT中的相关突变。

家族性高胆固醇血症（FHC）的特征在于血清胆汁酸浓度升高，瘙痒和脂肪吸收不良。我们在这里显示，阿米什人中的FHC与紧密连接蛋白2（由TJP2编码，也称为ZO-2编码）和胆汁酸辅酶A：氨基酸N-酰基转移酶（由BAAT编码）的突变相关。在第一个PDZ结构域中发生的TJP2突变会降低结构域稳定性和体外配体结合。我们注意到肝紧密连接的形态变化。胆汁酸结合酶BAAT的突变消除了酶的活性。关于该突变纯合的个体的血清仅包含未结合的胆汁酸。TJP2和BAAT中的突变都可能破坏胆汁酸的运输和循环。继承似乎是寡生的，