PDF(Pubmed)
Abstract：
UNASSIGNED: Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly of unknown etiology, although, genetic and environmental factors have been associated with its development. Variants in several genes expressed in the urogenital pathway have been reported as causative for bladder exstrophy in human and murine models. The expansion of next-generation sequencing and molecular genomics has improved our ability to identify the underlying genetic causes of similarly complex diseases and could thus assist with the investigation of the molecular basis of BEEC.
UNASSIGNED: The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population.
UNASSIGNED: We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as \"sufficient\" or \"insufficient\" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC.
UNASSIGNED: Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient.
UNASSIGNED: We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition.
UNASSIGNED: The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population.
UNASSIGNED: We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as \"sufficient\" or \"insufficient\" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC.
UNASSIGNED: Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient.
UNASSIGNED: We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition.
摘要：
■膀胱外翻外翻综合征（BEEC）是一种病因不明的罕见先天性异常，虽然,遗传和环境因素与它的发展有关。据报道，在泌尿生殖途径中表达的几种基因的变体是人类和小鼠模型中膀胱外翻的原因。下一代测序和分子基因组学的扩展提高了我们识别类似复杂疾病的潜在遗传原因的能力，因此可以帮助研究BEEC的分子基础。
■目的是确定先前与膀胱外翻有关的基因中罕见杂合变体的存在，并将它们与我们研究人群中膀胱再生的存在或不存在相关联。
■我们介绍了12例BEEC患者的病例系列，这些患者在膀胱颈重建术或膀胱扩大术期间由儿科泌尿科进行了膀胱活检。根据膀胱体积大于或小于预期膀胱大小的40％，将病例分类为“足够”或“不足”（分别为5和7）。对照膀胱组织标本是从接受活检的患者（n=6）获得的，这些患者的情况不是膀胱外翻。对从膀胱标本分离的DNA进行全外显子组测序。基于从头突变的假设，以及具有不完全外显率的常染色体显性条件的潜在含义，对每例病例进行了常染色体显性变异的评估,这些变异的一组基因先前与BEEC有关.
■我们对文献的回顾确定了44个与人类膀胱外翻模型有关的基因。我们的整个外显子组测序数据分析在分类为足够的病例中确定了其中两个基因的罕见变异，在被归类为不足的病例中，其中五个基因中的七个变异。
■我们在我们的BEEC标本中发现了七个先前涉及的基因中的罕见变异。需要进一步的研究来进一步了解这种潜在的遗传异质性胚胎条件的细胞信号传导。
■目的是确定先前与膀胱外翻有关的基因中罕见杂合变体的存在，并将它们与我们研究人群中膀胱再生的存在或不存在相关联。
■我们介绍了12例BEEC患者的病例系列，这些患者在膀胱颈重建术或膀胱扩大术期间由儿科泌尿科进行了膀胱活检。根据膀胱体积大于或小于预期膀胱大小的40％，将病例分类为“足够”或“不足”（分别为5和7）。对照膀胱组织标本是从接受活检的患者（n=6）获得的，这些患者的情况不是膀胱外翻。对从膀胱标本分离的DNA进行全外显子组测序。基于从头突变的假设，以及具有不完全外显率的常染色体显性条件的潜在含义，对每例病例进行了常染色体显性变异的评估,这些变异的一组基因先前与BEEC有关.
■我们对文献的回顾确定了44个与人类膀胱外翻模型有关的基因。我们的整个外显子组测序数据分析在分类为足够的病例中确定了其中两个基因的罕见变异，在被归类为不足的病例中，其中五个基因中的七个变异。
■我们在我们的BEEC标本中发现了七个先前涉及的基因中的罕见变异。需要进一步的研究来进一步了解这种潜在的遗传异质性胚胎条件的细胞信号传导。
