胱氨酸尿症（cystinuria，CSNU）是临床少见遗传病，由溶质载体家族3成员1（Solute Carrier Family3 Member 1，SLC3A1）和溶质载体家族7成员9（Solute Carrier Family 7 Member 9，SLC7A9）两个基因突变导致。CSNU患者基因突变及基因分型一直备受临床关注，本文针对CSNU相关基因SLC3A1和SLC7A9的遗传突变情况、基因型-表型相关性及近期新药研究进展作一综述。

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田淑琳,刘薇,宋岩.胱氨酸尿症相关基因 SLC3A1 与 SLC7A9 突变与药物研究进展[J].泌尿外科杂志(电子版),2024,16(04):49-54.DOI:10.20020/j.CNKI.1674-7410.2024.04.10

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胱氨酸尿症（cystinuria，CSNU）是一种少见的遗传性疾病，全球流行率仅为1/7000，该疾病受种族和地理位置影响，流行性调查结果差异较大^[1-2]。胱氨酸结石症是CSNU最常见的临床表现，多数患者在20岁前发病^[3]。该类结石复发速度快，频率高，5年内复发率达80%，且损害肾功能，最终发展为慢性肾病，对人体造成不可逆的损害^[4-6]。胱氨酸结石分别占成人结石和儿童结石的1%~2%和6%~28%，中国胱氨酸结石患者构成比为0.57%，甚至更低^[4,7]。受多种因素局限，现有治疗方法无法根治该疾病。CSNU是一种常染色体遗传病，患者通常有家族遗传史。本文针对与CSNU相关的两种基因溶质载体家族3成员1（Solute Carrier Family 3 Member 1，SLC3A1）和溶质载体家族7成员9（Solute CarrierFamily 7 Member 9，SLC7A9）的遗传突变情况、基因型-表型相关性以及的近年来新药研究进展作一综述。

1 胱氨酸转运蛋白与相关编码基因 SLC3A1、SLC7A9

2 进展分型与临床分型对应关系

2.1 传统临床分型方法

2.2 基因分型方法

3 突变情况

3.1 基因分析

3.2 患者基因型-表型关联性

4 新型药物研究进展

4.1 L-胱氨酸二甲酯和 L-胱氨酸甲酯

4.2 ALA

4.3 硒

4.4 托伐普坦

5 小结与展望

CSNU受人群、种族的影响，基因突变率也有很大差异，应建立针对不同地区人群的基因数据库，了解不同人群间的差异。临床上不同基因型患者无法仅根据症状来区分，须行测序获取患者基因型，这可能与基因分组有关。在未来，可以开展新的分组方式探寻基因型-表型关联性以利于临床针对性治疗，尤其在基因治疗中通过CRISPR进行特定点位基因的改造和纠偏，也将是热点研究方向。部分有症状CSNU患者未检测到突变，可能存在外显子存在嵌入内含子的剪接位点突变被遗漏的现象，未来可以此为切入点进行基因测序。在多种药物精准递送方面，利用纳米技术等将分子靶点药物进行精准递送也是分子遗传病的前沿应用^[56]。

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