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.
擅长诊治各种危急重症烧伤、烧伤后疤痕挛缩、功能畸形整复、各类急慢性伤口、复杂难愈性创面、伤口早期微创美容及早期抗疤治疗等
浙江大学临床医学二系教授，浙江大学医学院附属第二医院主任医师，毕业于日本金泽医科大学。
主要从事烧伤早期损害发生机理与临床防治研究，作为项目负责人，先后主持国家杰出青年科学基金、国家自然科学基金重点项目、2项国家"973"课题、教育部创新团队发展计划项目、军队"十五"和"十一五" 指令性(专项)课题等20余项课题研究任务
对各类型急慢性创面如烧伤、褥疮、下肢血管性溃疡、糖尿病足溃疡、慢性骨髓炎、手术后创面不愈、放射性溃疡等疾病的诊断和治疗方面有一定临床经验，擅长慢性骨髓炎的诊疗。医学硕士，毕业于上海交通大学医学院骨科学硕士，现任上海交通大学医学院附属第九人民医院创面修复科住院医师，主要从事九院创面修复科的临床工作。
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。
