MOLECULAR GENETIC ANALYSIS OF VESICOURETERAL REFLUX IN PATIENTS & THEIR FAMILIES

像大多数泌尿生殖系统异常一样，膀胱输尿管反流似乎有多因素的起源，尽管遗传因素无疑存在。与正常人群相比，反流患者的兄弟姐妹发生反流的风险要大得多。高达50%的兄弟姐妹被注意到有反流。值得注意的是，大多数人(75%)没有症状。与一些早期研究的发现相反，索引患者的反流级别与他们的兄弟姐妹的反流级别似乎没有关系。指标病例中肾脏疤痕的存在可能也没有人们曾经认为的那么重要。拟议的临床研究旨在确定与膀胱输尿管反流有关的关键区域，并确定该区域中的其他基因；建立DNA和来自反流患者及其家庭成员的血液样本的储存库，用于连锁和突变分析；确定这些个体中是否存在染色体缺失，并确定已确定的缺失/突变的大小和位置。血液样本将在诊所就诊期间从患者及其直系亲属那里获得。抽血量将取决于受试者的年龄，并将是适当的数量，以分离DNA和RNA。分子遗传分析将在儿童医院基因组图谱设施中进行。样本将被等量提取DNA，并可能建立永生细胞系。将获得谱系信息。

Like most genitourinary anomalies, vesicoureteral reflux appears to have a multifactorial origin, although a genetic component undoubtedly exists. Siblings of patients with reflux have a much greater risk of having reflux than the normal population. Up to 50% of siblings have been noted to have reflux. Notably, the large majority (75%) are asymptomatic. Contrary to the findings in some earlier studies, there appears to be no relationship between the grade of reflux in index patients and that in their siblings. The presence of renal scars in the index case is probably also less important than was once supposed. The proposed clinical study aims to identify the critical region involved in vesicoureteral reflux and identify additional genes in the region; to establish a repository of DNA and blood samples from patients with reflux and their family members for the purpose of linkage and mutational analysis; and to determine the presence or absence of deletions of chromosomes in these individuals and determine the size and location of identified deletions/mutations. Blood samples will be obtained from patients and their immediate family during a clinic visit. The amount of blood drawn will depend on the age of the subject, and will be an amount appropriate for the isolation of DNA and RNA. Molecular genetic analysis will be performed in the Children's Hospital Genome Mapping Facility. Samples will be aliquoted for DNA extraction and possible establishment of immortalized cell lines. Pedigree information will be obtained.