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.
医学博士,教授、博士生导师,现任上海交通大学医学院科技发展处副处长、上海市烧伤研究所副所长。
现任解放军第三O四医院全军创伤修复重点实验室主任,全军烧伤研究所副所长兼基础研究部主任。主要领域涉及创伤弹道学、生长因子生物学、干细胞诱导分化与组织再生、严重创伤重要内脏缺血性损伤的主动修复与再生等长期从事创伤和创伤后。
主任护师;国际造口治疗师; 东莞市大朗医院护理部副主任; 东莞市护理学会伤口造口护理专业委员会主任委员; 广东省护士协会伤口造口失禁护士分会副会长; 广东省护理学会造口护理专业委员会常务委员; 中华预防医学会组织感染与损伤与控制专业委员会青委会 委员;
擅长:擅长骨与关节疾病的分期最优化及综合治疗,包括骨创伤、周围神经损伤、退行性骨关节炎、骨质疏松症、强直性脊柱炎及痛风等。在骨与软组织肿瘤领域有较高声誉,包括骨肉瘤的保肢治疗,骨巨细胞瘤的微创治疗,骨转移癌的综合治疗及肿瘤精准医疗领域有独到创新。
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。