Li Chuangye, Yang Yongjia, Zheng Yu, Shen Fang, Liu Li, Li Yanfang, Li Liping, Zhao Yaowang
Department of Urology, Hunan Children's Hospital, Changsha, China.
The Laboratory of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, University of South China, Changsha, China.
Front Genet. 2020 Feb 18;11:74. doi: 10.3389/fgene.2020.00074. eCollection 2020.
Cystinuria is a rare genetic disorder characterized by defective renal reabsorption of cystine, ornithine, arginine, and lysine. The increased urinary excretion of cystine results in the development of cystine urolithiasis (CU). The mutated and genes are the cause of CU, a global disorder. Its frequency and mutation spectrum vary between different populations. In Asia, the data for CU are limited.
Urinary stones were collected from patients of a single center over a five-year period and analyzed Fourier transform infrared spectroscopy. Genomic DNA was isolated from 13 patients with CU and their parents and from 26 controls affected by calcium oxalate dihydrate stones. The coding regions and the exon-intron boundaries of and were subjected to PCR amplification and then sequenced traditional Sanger sequencing. Genetic variants were functionally annotated using the InterVar, ClinVar, gnom AD, and HGMD databases.
From the 232 samples of urinary stones, we identified 13 patients with CU (10 males and 3 females). The onset age was from 7 months to 9 years. The CU stones varied from 0.26 cm to 18.67 cm. Sanger sequencing detected a total of 14 (nine were novel) and 10 (six were novel) rare variants from the 13 CU families. All variants, including 15 novel variants, were pathogenic, disease-causing, or damaging.
All 13 pediatric CU families harbored or/and rare variants. A total of 15 novel pathogenic variants in and were identified. This study expanded the known mutational spectrum of CU in the Chinese population.
胱氨酸尿症是一种罕见的遗传性疾病，其特征为肾脏对胱氨酸、鸟氨酸、精氨酸和赖氨酸的重吸收存在缺陷。胱氨酸尿排泄增加导致胱氨酸尿路结石（CU）的形成。突变的 和 基因是导致CU这种全球性疾病的原因。其发病率和突变谱在不同人群中有所不同。在亚洲，关于CU的数据有限。
在五年期间从一个单一中心的患者中收集尿结石，并通过傅里叶变换红外光谱进行分析。从13例CU患者及其父母以及26例受二水合草酸钙结石影响的对照者中分离基因组DNA。对 和 的编码区以及外显子 - 内含子边界进行PCR扩增，然后通过传统的桑格测序法进行测序。使用InterVar、ClinVar、gnomAD和HGMD数据库对遗传变异进行功能注释。
在232份尿结石样本中，我们鉴定出13例CU患者（10例男性和3例女性）。发病年龄从7个月至9岁不等。CU结石大小从0.26厘米至18.67厘米不等。桑格测序从13个CU家族中总共检测到14个 （9个为新发现的）和10个 （6个为新发现的）罕见变异。所有变异，包括15个新发现的变异，均为致病、致病变异或有害变异。
所有13个儿科CU家族均携带 或/和 罕见变异。在 和 中总共鉴定出15个新的致病变异。本研究扩展了中国人群中已知的CU突变谱。
