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:各种创伤、骨质疏松症及骨质疏松性骨折、颈肩腰腿痛的诊断和治疗(腰椎间盘突出症的微创治疗);致力于骨质疏松性骨折防治的基础与临床研究,主持国家自然科学基金、省级课题及校级课题各1项。广州华侨医院骨科主治医师、骨科学博士、科学型硕士生导师。
擅长断肢(指、趾、鼻、耳、阴茎)再植和再造手术、各种组织修复和皮瓣移植、严重复杂性创伤伴多发骨折、血管神经损伤的急救与早期处理和二期功能重建、先天性畸形及烧伤瘢痕挛缩畸形矫正、美容整形等
擅长疾病:糖尿病足;慢性、难愈合性伤口治疗。执业经历:
擅长:擅长断指(肢)再植、游离足趾移植再造手指、周围神经血管损伤修复、各种组织瓣移植修复肢体组织缺损,在手部畸形、肿瘤及周围神经卡压等诊治方面有较丰富的临床经验。
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
扫一扫了解详情:
任何关于疾病的建议都不能替代执业医师的面对面诊断。所有门诊时间仅供参考,最终以医院当日公布为准。
网友、医生言论仅代表其个人观点,不代表本站同意其说法,请谨慎参阅,本站不承担由此引起的法律责任。