Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers:: A need for a new classification
Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers:: A need for a new classification
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DOI：
10.1097/01.asn.0000029586.17680.e5
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发表时间：
2002-10-01
影响因子：
13.6
通讯作者：
Rizzoni, G
中科院分区：
文献类型：
--
作者：
Dello Strologo, L;Pras, E;Rizzoni, G
胱氨酸尿的遗传学和生理学的最新进展不支持传统的分类，即基于专性杂合子中胱氨酸和二碱性氨基酸的排泄。国际胱氨酸尿协会（ICC）发现，只有两个基因（SLC3A1和SLC7A9）的突变导致了所有三种类型的疾病。ICC建立了一个跨国数据库，收集了224例胱氨酸尿病患者的遗传和临床数据，其中125例具有完整的基因型定义。189例具有遗传定义的杂合子和83例健康对照者的氨基酸尿排泄模式也被纳入研究。所有SLC3A1携带者和14%的SLC7A9携带者显示正常的氨基酸尿型（即I型表型）。其余SLC7A9携带者为非i型（III型，80.5%；II型，5.5%）。这使得传统的分类不精确。需要一个新的分类：A型，由于2号染色体上SLC3A1 （rBAT）的两个突变（在我们的数据库中占45.2%）；B型，由于19号染色体上SLC7A9的两个突变（53.2%）；第三种可能是AB型（1.6%），上述基因各有一个突变。临床资料显示，男性胱氨酸尿症比女性更为严重。两种类型的胱氨酸尿（A和B）在本回顾性研究中有相似的结果，但治疗效果无法分析。结石事件与尿中氨基酸排泄无关。17%的患者肾功能明显受损。
Recent developments in the genetics and physiology of cystinuria do not support the traditional classification, which is based on the excretion of cystine and dibasic amino acids in obligate heterozygotes. Mutations of only two genes (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC), have been found to be responsible for all three types of the disease. The ICC set up a multinational database and collected genetic and clinical data from 224 patients affected by cystinuria, 125 with full genotype definition. Amino acid urinary excretion patterns of 189 heterozygotes with genetic definition and of 83 healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9 carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II, 5.5%). This makes the traditional classification imprecise. A new classification is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2% in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2% in this series); and a possible third type, AB (1.6%), with one mutation on each of the above-mentioned genes. Clinical data show that cystinuria is more severe in males than in females. The two types of cystinuria (A and B) had a similar outcome in this retrospective study, but the effect of the treatment could not be analyzed. Stone events do not correlate with amino acid urinary excretion. Renal function was clearly impaired in 17% of the patients.