Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland
Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland
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DOI：
10.1080/0886022x.2019.1655452
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发表时间：
2019-01-01
期刊：
影响因子：
3
通讯作者：
Conlon, P. J.
中科院分区：
文献类型：
--
作者：
Cormican, S.;Connaughton, D. M.;Conlon, P. J.
简介：常染色体显性肾小管间质性肾病（ADTKD）是一种罕见的肾损害遗传原因，由MUC1、UMOD、HNF1B、REN和SEC61A1基因突变引起。这些疾病的国家或全球流行率尚未确定。我们旨在建立一个爱尔兰ADTKD患者的数据库，并报告这些家族的临床和遗传特征。研究方法：我们通过爱尔兰肾脏基因项目和转诊至博蒙医院国家肾脏遗传学诊所，确定了符合ADTKD临床标准（慢性肾脏疾病、温和尿沉渣和常染色体显性遗传）的患者。然后邀请符合条件的患者通过各种方法进行基因检测，包括基于小组的检测，全外显子组测序，并且在五个符合ADTKD诊断标准但因果基因突变阴性的家庭中，我们分析了尿细胞涂片中MUC1fs蛋白的存在。结果：共研究了16个家系的54名个体。我们在3个家庭中发现了MUC1基因突变，在5个家庭中发现了UMOD，在2个家庭中发现了HNF 1 β，在3个家庭中发现了尿涂片中存在异常MUC1蛋白（其中一个先前已知携带基因突变）。我们无法在4个家族中鉴定出突变（其中3个家族的尿MUC1fs检测也为阴性）。结论：爱尔兰有4443例终末期肾病患者，其中24例为本文所述队列的成员。我们观察到ADTKD至少占爱尔兰ESRD患者的0.54%。
Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.