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:脊柱外科、脊柱微创技术、显微创伤外科、腰椎间盘突出症脊柱侧弯等。
熟练掌握了骨科常见病、多发病及疑难病症的诊治技术,成功抢救了各种多发伤、多发骨折等急诊、危重病人。能够熟练应用各种新型内固定材料手术治疗四肢及关节复杂骨折、复杂骨盆及髋臼骨折、骨不连等,手外伤的急诊手术、关节置换及翻修术、关节镜下手术,以及骨肿瘤、脊柱手术等各类骨科手术、手术治疗效果良好。能够熟练应用DHS、DCS、PFNA、髋动力锁定钢板、各种交锁髓内钉、解剖钢板及Liss钢板治疗四肢及关节复杂骨折、复杂骨盆及髋臼骨折手术、骨不连手术及手外伤的急诊手术、关节置换及翻修术、膝关节镜下半月板切除及交叉韧带重建术,以及骨肿瘤、脊柱手术等各类骨科手术、对创伤骨科微创治疗具有丰富的临床经验。
临床工作经验丰富,具有极为熟练的外科技能,在骨科各领域有较深的造诣。尤其在关节外科方面,已开展全身六大关节的关节镜检查和镜下手术,总体水平在广东领先,率先在广东开展关节镜下膝关节前、后交叉韧带重建术、膝关节半月板修补术、关节内骨折关节镜监视下复位固定术等高难度手术。并已开展四肢大关节的人工关节置换术,被广东省定为人工关节置换术指导专家。在复杂关节畸形的人工关节置换方面颇有研究。
擅长:危重烧伤救治/重度吸入性损伤的救治/小儿重度烧伤救治/严重皮肤撕脱伤及复合伤救治/烧伤瘢痕整复及功能重建/糖尿病足保肢治疗。
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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