Glenda M. Beaman a,b, Adrian S. Woolf c,d, Filipa M. Lopes c, Shuang Andrew Guo e,f,g, J. Robert Harkness a,b, Raimondo M. Cervellione d, David Keene d, Imran Mushtaq h, Menna R. Clatworthy f,g,h, William G. Newman a,b,*
Summary
Introduction
Bladder exstrophyeepispadias complex (BEEC) comprises a spectrum of anterior midline congenital malformations, involving the lower urinary tract. BEEC is usually sporadic, but families with more than one affected member have been reported, and a twin concordance study supported a genetic contribution to pathogenesis. Moreover, diverse chromosomal aberrations have been reported in a small subset of individuals with BEEC. The commonest are 22q11.2 microduplications, identified in approximately 3% of BEEC index cases.
Objectives
We aimed to refine the chromosome 22q11.2 locus, and to determine whether the encompassed genes are expressed in normal developing and mature human urinary bladders.
Results
Using DNA from an individual with CBE, the 22q11.2 duplicated locus was refined by identification of a maternally inherited 314 kb duplication (chr22:21,147,293e21,461,017), as depicted in this image. Moreover, the eight protein coding genes within the locus were found to be expressed during normal developing and mature bladders. To determine whether duplications in any of these individual genes were associated with CBE, we undertook copy number analyses in 115 individuals with CBE without duplications of the whole locus. No duplications of individual genes were found.
Discussion
The current study has refined the22q11.2locus associated with BEEC and has shown that the eight protein coding genes are expressed in human bladders both during antenatal development and postnatally. Nevertheless, the precise biological explanation as to why duplication of the phenocritical region of22q11 confers increased susceptibility to BEEC remains to be determined. The fact that individuals with CBE without duplications of the whole locus also lacked duplication of any of the individual genes suggests that in individuals with BEEC and duplication of the 22q11.2 locus altered dosage of more than one gene may be important in BEEC etiology.
Conclusions
The study has refined the 22q11.2 locus associated with BEEC and has shown that the eight protein coding genes within this locus are expressed in human bladders.
擅长领域:介入微创诊疗血管性疾病等,如下肢动脉硬化闭塞症、糖尿病足、血管畸形、静脉曲张、动静脉血栓形成、静脉狭窄闭塞等。
东莞康华医院国际造口治疗师,采用全球倡导的伤口湿性愈合疗法和造口专科护理新技术,在糖尿病溃疡足、下肢动/静脉溃疡、骨髓炎、外科术后感染/脂肪液化、肿瘤伤口、放射性皮炎、痛风破溃感染、压力性损伤(压疮)、液体外渗、造口并发症、失禁、瘘管等方面提供专业化的诊治、咨询及健康教育。
从事骨科临床工作和外科学教学工作30年。擅长骨关节疾病、四肢骨折和手外伤的保守治疗、手术治疗(关节置换手术、四肢骨折内固定手术、创伤修复手术);各类创面的修复:包括糖尿病足、难治性痛风破溃感染伤口、创伤术后伤口不愈合。
长期从事影像诊断和介入放射学诊疗工作,擅长肿瘤和血管病的介入治疗。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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