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.
擅长疾病:在烧伤、创伤后瘢痕整形、先天性畸形、面部及躯干美容等方面临床经验丰富,具有较强的解决本专业疑难病例的能力及显微外科手术能力。
擅长领域:(1)耳廓、乳房、阴茎、鼻部等体表器官再造(2)体表软组织肿瘤切除与美容修复(3)脂肪移植与面部年轻化(4)血管瘤、鲜红斑痣等激光美容
对烧伤外科、整形外科及美容外科有较深的造谐,擅长大面积严重烧伤的救治,唇腭裂修复、软组织缺损的修复及各类美容整形和再造整形手术,每年完成大小各类手术360余例。
从事整形外科近30年,留美多年,熟练掌握面部美容、除皱、乳房整形、脂肪抽吸等各类美容整形外科手术及各种非手术美容(如肉毒毒素A注射除皱等),对外生殖器整形与再造,两性畸形和易性症的手术治疗等有较深入研究。
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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