Vaz Frédéric M, Huidekoper Hidde H, Paulusma Coen C
Laboratory Genetic Metabolic Disease, Academic Medical Center, Amsterdam, The Netherlands.
Dig Dis. 2017;35(3):259-260. doi: 10.1159/000450984. Epub 2017 Mar 1.
We present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation. This confirms the role of NTCP as the major transporter of conjugated bile salts into the liver as part of the enterohepatic circulation and shows that other transporters partly can take over its function, resulting in a relatively mild phenotype. This work was published previously in [Vaz et al.: Hepatology 2015;61:260-267] and supplemented with some follow-up information of the patient.
我们报告了首例钠-牛磺胆酸盐共转运多肽SLC10A1（NTCP）存在缺陷的患者，该蛋白在胆盐的肠肝循环中起关键作用。患儿临床表现轻微，尽管血浆胆盐水平极度升高（超过正常上限100倍），但未表现出肝功能障碍或瘙痒迹象。在SLC10A1基因中发现了一个纯合点突变（导致氨基酸变化R252H），功能研究证实了该突变的致病性。这证实了NTCP作为结合型胆盐进入肝脏作为肠肝循环一部分的主要转运体的作用，并表明其他转运体可部分替代其功能，从而导致相对较轻的表型。这项工作先前发表于[Vaz等人：《肝脏病学》2015年；61:260 - 267]，并补充了该患者的一些随访信息。
