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:在烧伤、整形临床工作中擅长治疗各种原因所致的烧伤、增生性瘢痕引起的畸形(疤痕磨削后Recell技术的应用及复合皮移植技术的应用)、皮肤慢性溃疡或难愈伤口、软组织损伤和缺损。承担放心120-全国最佳医院、广东省重点学科、特重烧伤救治知名专家。先后共开展4项新技术治疗。已招收培养16名硕士研究生,8名博士研究生。
现任中国医师协会烧伤科医师分会会长、中华烧伤杂志总编辑、全军烧伤外科专业委员会委员、重庆市烧伤专业委员会前任主任委员。
美国哈佛大学烧伤中心访问学者,全军烧伤专业委员会 常务委员,全国烧伤外科学分会青年委员会副主任委员,解放军医学杂志编委,中华烧伤杂志通讯编委。 擅长危重烧伤、颜面部烧伤、深度电烧伤和糖尿病足等难愈性创面治疗,特别是在疤痕与畸形整复方面经验丰富。
现任中华医学会创伤分会创面学组全国委员、中国医师学会烧伤分会全国委员、中华医学会烧伤分会青年委员、全军烧伤专业委员会委员、重庆市烧伤专业委员会委员、西南五省一巿烧伤整形学术委员会常委、中华烧伤杂志通讯编委、国家自然基金及SFDA新药评审专家、国外SCI杂志BURNS及Military Medicine等杂志审稿人等。
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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