The genetic diversity of cystinuria in a UK population of patients
The genetic diversity of cystinuria in a UK population of patients
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DOI：
10.1111/bju.12894
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发表时间：
2015-07-01
影响因子：
4.5
通讯作者：
Thomas, Kay
中科院分区：
文献类型：
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作者：
Wong, Kathie A.;Mein, Rachael;Thomas, Kay
目的检查英国第一批胱氨酸尿症患者的基因突变，并初步确定基因型/表型相关性。患者和方法采用 DNA 测序和多重连接依赖性探针扩增 (MLPA) 技术对英国胱氨酸尿症专科诊所的 74 名患者进行了突变鉴定。 A型胱氨酸尿症患者被分为两组：M组患者至少有一种错义突变，N组患者有所有其他类型突变的两个等位基因，包括移码、剪接位点、无义、缺失和重复。使用Mann-Whitney U检验比较两组患者的尿二碱基氨基酸水平、发病年龄、结石发作次数和干预措施。结果共有41名患者患有A型胱氨酸尿症，其中1名患者患有意义不明的变异，23名患者患有B型胱氨酸尿症，其中6名患者患有意义不明的变异。一名患者的 SLC7A9 存在 3 个序列变异；然而，其中有两个意义不明。 3 名患者患有 AB 型胱氨酸尿症。其中三人的 SLC7A9 存在单一突变。在三名患者的任一基因中均未发现已发现的突变。 SLC3A1共有88个突变，SLC7A9共有55个突变。在我们的英国患者队列中发现了 23 种先前未发表的致病突变。在 A 型胱氨酸尿症患者中，错义突变的存在与尿赖氨酸水平较低相关（平均 [SE] 611.9 [22.65] vs 752.3 [46.39] 毫摩尔每摩尔肌酐 [mM/MC]；P=0.02）、精氨酸（194.8 [24.83] vs 397.7 [15.32]）毫米/MC;
ObjectiveTo examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation.Patients and MethodsDNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK. Patients with type A cystinuria were classified into two groups: Group M patients had at least one missense mutation and Group N patients had two alleles of all other types of mutations including frameshift, splice site, nonsense, deletions and duplications. The levels of urinary dibasic amino acids, age at presentation of disease, number of stone episodes and interventions were compared between patients in the two groups using the Mann-Whitney U-test.ResultsIn all, 41 patients had type A cystinuria, including one patient with a variant of unknown significance and 23 patients had type B cystinuria, including six patients with variants of unknown significance. One patient had three sequence variants in SLC7A9; however, two are of unknown significance. Three patients had type AB cystinuria. Three had a single mutation in SLC7A9. No identified mutations were found in three patients in either gene. There were a total of 88 mutations in SLC3A1 and 55 mutations in SLC7A9. There were 23 pathogenic mutations identified in our UK cohort of patients not previously published. In patients with type A cystinuria, the presence of a missense mutation correlated to lower levels of urinary lysine (mean [SE] 611.9 [22.65] vs 752.3 [46.39] millimoles per mole of creatinine [mM/MC]; P=0.02), arginine (194.8 [24.83] vs 397.7 [15.32] mM/MC; P