Skopková Zuzana, Hrabincová Eva, Stástná Sylvie, Kozák Libor, Adam Tomás
Laboratory of Inhented Metabolic Disorders, Department of Clinical Chemistry, Palacký University and Hospital, Olomouc, Czech Republic.
Ann Hum Genet. 2005 Sep;69(Pt 5):501-7. doi: 10.1111/j.1529-8817.2005.00185.x.
Cystinuria is a frequently inherited metabolic disorder in the Czech population (frequency 1/5,600) caused by a defect in the renal transport of cystine and dibasic amino acids (arginine, lysine and ornithine). The disease is characterized by increased urinary excretion of the amino acids and often leads to recurrent nephrolithiasis. Cystinuria is classified into two subtypes (type I and type non-I). Type I is caused predominantly by mutations in the SLC3A1 gene (2p16.3), encoding heavy subunit (rBAT) of the heterodimeric transporter. Cystinuria non-I type is caused by mutations in the SLC7A9 gene (19q13.1). In this study, we present results of molecular genetic analysis of the SLC3A1 and the SLC7A9 genes in 24 unrelated cystinuria families. Individual exons of the SLC3A1 and SLC7A9 genes were analyzed by direct sequencing. We found ten different mutations in the SLC3A1 gene including six novel ones: three missense mutations (G140R), D179Y and R365P), one splice site mutation (1137-2A>G), one deletion (1515_1516delAA), and one nonsense mutation (Q119X). The most frequent mutation, M467T; was detected in 36% of all type I classified alleles. In the SLC7A9 gene we found six mutations including three new ones: one missense mutation (G319R), one insertion (611_612insA) and one deletion (205_206delTG). One patient was compound heterozygote for one SLC3A1 and one SLC7A9 mutation. Our results confirm that cystinuria is a heterogeneous disorder at the molecular level, and contribute to the understanding of the distribution and frequency of mutations causing cystinuria in the Caucasian population.
胱氨酸尿症是捷克人群中一种常见的遗传性代谢紊乱疾病（发病率为1/5600），由肾脏对胱氨酸和二碱基氨基酸（精氨酸、赖氨酸和鸟氨酸）的转运缺陷引起。该疾病的特征是氨基酸尿排泄增加，常导致复发性肾结石。胱氨酸尿症分为两种亚型（I型和非I型）。I型主要由SLC3A1基因（2p16.3）突变引起，该基因编码异二聚体转运蛋白的重链亚基（rBAT）。非I型胱氨酸尿症由SLC7A9基因（19q13.1）突变引起。在本研究中，我们展示了对24个无关的胱氨酸尿症家族的SLC3A1和SLC7A9基因进行分子遗传学分析的结果。通过直接测序分析了SLC3A1和SLC7A9基因的各个外显子。我们在SLC3A1基因中发现了10种不同的突变，包括6种新突变：3种错义突变（G140R、D179Y和R365P）、1种剪接位点突变（1137-2A>G）、1种缺失突变（1515_1516delAA）和1种无义突变（Q119X）。最常见的突变M467T在所有I型分类等位基因中占36%。在SLC7A9基因中，我们发现了6种突变，包括3种新突变：1种错义突变（G319R）、1种插入突变（611_612insA）和1种缺失突变（205_206delTG）。1名患者为1种SLC3A1突变和1种SLC7A9突变的复合杂合子。我们的结果证实，胱氨酸尿症在分子水平上是一种异质性疾病，并有助于了解导致白种人群胱氨酸尿症的突变分布和频率。
