Urinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 (DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of DCHS1. Children with (n = 370) and without (n = 71) VUR from two well-phenotyped clinical trials of UTI were copy-typed and compared to 491 healthy controls with no known history of VUR or UTI. Less than 1% of controls had a single copy of DCHS1, while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the DCHS1 gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic Escherichia coli strains, and Dchs1 mRNA was quantified. This study represents the first report of DCHS1 in association with pediatric UTI. We hypothesize that its role in innate immunity is critical to lower urinary tract defense. Further investigation is required to determine the role of DCHS1 in innate immunity.

与膀胱输尿管反流 (VUR) 相关的尿路感染 (UTI) 可导致慢性肾脏疾病。先天免疫防御的遗传改变会导致 UTI 风险。我们研究了UTI 儿童中的一种新基因 Dachsous Cadherin-Related 1 ( DCHS1 )。我们确定了 UTI 儿童DCHS1 的绝对 DNA 拷贝数 (CN) 。在这项病例对照研究中，我们利用多种互补方法来确定DCHS1的基因组 CN 。 来自两项 UTI 表型良好的临床试验中患有 ( n  = 370) 和没有 ( n = 71) VUR 的儿童进行了复制分型，并与 491 名没有已知 VUR 或 UTI 病史的健康对照进行了比较。不到 1% 的对照具有DCHS1的单个副本，而 31% 的 UTI 和无 VUR 儿童和 7% 的 UTI 和 VUR 儿童具有单拷贝DCHS1基因。使用免疫染色，我们在出生后将表达定位到膀胱和肾上皮细胞。小鼠也受到两种尿路致病性大肠杆菌菌株的挑战，并对Dchs1 mRNA 进行了量化。这项研究代表了DCHS1与儿科 UTI 相关的第一份报告。我们假设它在先天免疫中的作用对于下尿路防御至关重要。需要进一步研究以确定DCHS1在先天免疫中的作用。