Rotor综合征患儿4例的临床特征及遗传学分析

Clinical characteristics and genetic analysis of four children with Rotor syndrome

目的:探讨4例Rotor综合征患儿SLCO1B1/SLCO1B3基因的变异特点,为临床诊疗和遗传咨询提供依据。方法:以2019年1月至2022年1月湖南省儿童医院肝病科收治的4例患儿作为研究对象,对其进行家系全外显子组测序分析,并用凝胶电泳法对长散布元件-1(LINE-1)插入变异进行验证。结果:4例患儿均表现为皮肤及巩膜黄染。基因检测提示其SLCO1B1基因存在3处变异,分别为c.1738C>T(p.R580*)、c.757C>T(p.R253*)以及c.1622A>C(p.Q541P);SLCO1B3基因存在2处变异,分别为c.481+22insLINE-1及c.1747+1G>A。3例患儿携带SLCO1B1/SLCO1B3基因纯合变异,1例携带复合杂合变异。Sanger测序证实了上述变异的存在,凝胶电泳实验证实4例患儿均携带SLCO1B3基因第6内含子约6 kb的LINE-1插入变异。结论:4例Rotor综合征患儿均由SLCO1B1/SLCO1B3基因的变异所致。SLCO1B3基因LINE-1插入变异可能是中国Rotor患者中常见的变异类型。

Objective To explore the characteristics of SLCO1B1/SLCO1B3 gene variants among children with Rotor syndrome(RS).Methods Four children who were admitted to the Department of Hepatology of Hunan Children′s Hospital between January 2019 and January 2022 were selected as the study subjects.Trio-whole exome sequencing was carried out for the four families,and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1(LINE-1).Results Genetic testing has identified three variants of the SLCO1B1 gene,including c.1738C>T(p.R580*),c.757C>T(p.R253*)and c.1622A>C(p.Q541P),and two variants of the SLCO1B3 gene,including c.481+22insLINE-1 and c.1747+1G>A among the children.Three of them were found to harbor homozygous variants of the SLCO1B1/SLCO1B3 genes,and one has harbored compound heterozygous variants.Sanger sequencing confirmed the existence of all variants,and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children.Conclusion The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/SLCO1B3 genes.The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.