Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease
Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease
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DOI：
10.1186/s12882-018-1107-y
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发表时间：
2018-10-30
期刊：
影响因子：
2.3
通讯作者：
Venkat-Raman, G.
中科院分区：
文献类型：
--
作者：
Gast, Christine;Marinaki, Anthony;Venkat-Raman, G.
背景常染色体显性遗传性肾小管间质性肾病（ADTKD）是由UMOD基因突变引起的一种罕见疾病，目前尚不清楚。我们的目的是建立流行的遗传性肾脏疾病，ADTKD和ADTKD-UMOD在成人慢性肾脏病（CKD）patients.MethodsWe调查的特点发送问卷的家族史，所有患者的CKD阶段3-5在我们的三级肾脏中心，以确定患者遗传性肾脏疾病。从患者访谈和临床记录中获得有关临床和家族史的详细信息。结果3770份调查问卷中，回收2027份。459例患者报告了家族史，其中217例患者与遗传性肾病一致。通过数据库检索确定了182例遗传性肾病无应答者。在这399例患者中，252例患有常染色体显性多囊肾病（ADPKD），28例患有ADTKD，25例患有Alport，44例未知，导致11%的CKD 3-5患者和19%的终末期肾病患者患有遗传性肾病。在未知的患者中，有40人进行了基因分型，其中31人的发现与ADTKD一致。30%的未知ADTKD患者和39%的未知ADTKD患者存在UMOD突变。共有来自18个家族的3 - 5名个体被发现有10种不同的UMOD突变（3种新突变），占CKD 3-5患者的1%，占终末期肾病患者的2%，占遗传性肾病的9%，占ADTKD的56%。ADTKD-UMOD是继ADPKD之后最常见的遗传性肾病，人群患病率为9/100万。较少的蛋白尿和血尿，而不是高尿酸血症或痛风是ADTKD-UMOD的预测指标。该研究的主要局限性是单中心设计和主要是高加索population.ConclusionsThe遗传性肾脏疾病和ADTKD-UMOD的患病率显着高于以前描述的。临床特征对ADTKD-UMOD的预测性较差，突出了仅以家族史为指导进行基因检测的必要性。
BackgroundAutosomal dominant tubulointerstitial kidney disease (ADTKD) caused by mutations in the UMOD gene (ADTKD-UMOD) is considered rare and often remains unrecognised. We aimed to establish the prevalence of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.MethodsWe sent questionnaires on family history to all patients with CKD stages 3-5 in our tertiary renal centre to identify patients with inherited renal disease. Details on clinical and family history were obtained from patient interviews and clinical records. Sanger sequencing of the UMOD gene was performed from blood or saliva samples.Results2027 of 3770 sent questionnaires were returned. 459 patients reported a family history, which was consistent with inherited kidney disease in 217 patients. 182 non-responders with inherited kidney diseases were identified through a database search. Of these 399 individuals, 252 had autosomal dominant polycystic kidney disease (ADPKD), 28 had ADTKD, 25 had Alports, and 44 were unknown, resulting in 11% of CKD 3-5 patients and 19% of end-stage renal disease patients with genetic kidney diseases. Of the unknown, 40 were genotyped, of whom 31 had findings consistent with ADTKD. 30% of unknowns and 39% of unknowns with ADTKD had UMOD mutations. Altogether, 35 individuals from 18 families were found to have ten distinct UMOD mutations (three novel), making up 1% of patients with CKD 3-5, 2% of patients with end-stage renal disease, 9% of inherited kidney diseases and 56% with ADTKD. ADTKD-UMOD was the most common genetic kidney disease after ADPKD with a population prevalence of 9 per million. Less proteinuria and haematuria, but not hyperuricaemia or gout were predictive of ADTKD-UMOD. The main limitations of the study are the single-centre design and a predominantly Caucasian population.ConclusionsThe prevalence of genetic kidney diseases and ADTKD-UMOD is significantly higher than previously described. Clinical features poorly predicted ADTKD-UMOD, highlighting the need for genetic testing guided by family history alone.