Molecular bases of congenital bladder disease: the urofacial syndome (UFS)

先天性膀胱疾病的分子基础：尿面综合征（UFS）

• 批准号: MR/L002744/1
• 负责人: Adrian Woolf
• 金额: $ 64.69万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL002744%2F1
• 关键词: Molecular; bases; congenital; bladder; disease

In the UK, there are 3,000-5,000 people who were born with abnormal kidneys and/or bladders who have such severe kidney failure that they can only survive by having regular dialysis or kidney transplants. The is increasing evidence that such individuals carry abnormalities of genes which normally help the bladder and kidney grow before birth. Finding the specific genetic causes of such disorders provides families with often long-sought answers to the question "why was our child born with kidney disease". The urofacial syndrome is a specific disease in which urinary bladder muscle does not behave normally. The condition starts before birth and people with the disease suffer life-long urinary incontinence and have a high risk of developing kidney failure. We were the first to describe changes in two genes responsible for this disease. Affected children inherit two copies of an altered gene, one from each parent, who themselves are healthy. We believe that the normal function of these genes is to help the growth of nerves into the bladder and that these nerves control the filling and emptying of the bladder. In this project we will search for other genes which cause the the urofacial syndrome and related conditions. These include 'primary vesicoureteric reflux', the backwards movement of urine from bladder to kidney, a condition which affects around 1 in 100 of all babies. To understand why these diseases happen, and what the genes do, we are studying models of the human condition. We will test novel treatments in these models with the aim of similar treatments being used in the future to treat people with bladder disease.

在英国，有3，000 - 5，000人出生时就有异常的肾脏和/或膀胱，他们患有严重的肾衰竭，只能通过定期透析或肾移植来生存。越来越多的证据表明，这些人携带的基因异常，通常有助于膀胱和肾脏在出生前的增长。找到这些疾病的特定遗传原因为家庭提供了长期寻求的问题答案“为什么我们的孩子出生时患有肾病”。尿面部综合征是一种特殊的疾病，其中膀胱肌肉不正常的行为。这种疾病在出生前就开始了，患有这种疾病的人会终生患有尿失禁，并且有很高的肾衰竭风险。我们是第一个描述导致这种疾病的两个基因的变化的人。受影响的儿童遗传了两个改变基因的拷贝，每个拷贝来自父母，而父母本身是健康的。我们认为这些基因的正常功能是帮助神经生长到膀胱中，这些神经控制膀胱的充盈和排空。在这个项目中，我们将寻找其他基因引起的urofacial综合征和相关的条件。这些包括“原发性膀胱输尿管反流”，尿液从膀胱向后运动到肾脏，这种情况影响大约1/100的婴儿。为了了解这些疾病发生的原因以及基因的作用，我们正在研究人类状况的模型。我们将在这些模型中测试新的治疗方法，目的是将来使用类似的治疗方法来治疗膀胱疾病。

项目成果

Pinpointing clinical diagnosis through whole exome sequencing to direct patient care: a case of Senior-Loken syndrome.

• DOI: 10.1016/s0140-6736(15)60496-2
• 发表时间: 2015-05-09
• 期刊: Lancet (London, England)
• 作者: Ellingford JM;Sergouniotis PI;Lennon R;Bhaskar S;Williams SG;Hillman KA;O'Sullivan J;Hall G;Ramsden SC;Lloyd IC;Woolf AS;Black GC
• 通讯作者: Black GC

Bridging the gap: functional healing of embryonic small intestine ex vivo.

• DOI: 10.1002/term.2073
• 发表时间: 2016-02
• 期刊: Journal of tissue engineering and regenerative medicine
• 影响因子: 3.3
• 作者: Coletta R;Roberts NA;Oltrabella F;Khalil BA;Morabito A;Woolf AS
• 通讯作者: Woolf AS

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

• DOI: 10.1038/ng.3681
• 发表时间: 2016-11
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Caubit, Xavier;Gubellini, Paolo;Andrieux, Joris;Roubertoux, Pierre L.;Metwaly, Mehdi;Jacq, Bernard;Fatmi, Ahmed;Had-Aissouni, Laurence;Kwan, Kenneth Y.;Salin, Pascal;Carlier, Michele;Lieden, Agne;Rudd, Eva;Shinawi, Marwan;Vincent-Delorme, Catherine;Cuisset, Jean-Marie;Lemaitre, Marie-Pierre;Abderrehamane, Fatimetou;Duban, Benedicte;Lemaitre, Jean-Francois;Woolf, Adrian S.;Bockenhauer, Detlef;Severac, Dany;Dubois, Emeric;Zhu, Ying;Sestan, Nenad;Garratt, Alistair N.;Goff, Lydia Kerkerian-Le;Fasano, Laurent
• 通讯作者: Fasano, Laurent

Expanding the HPSE2 Genotypic Spectrum in Urofacial Syndrome, A Disease Featuring a Peripheral Neuropathy of the Urinary Bladder.

• DOI: 10.3389/fgene.2022.896125
• 发表时间: 2022
• 期刊: Frontiers in genetics
• 影响因子: 3.7

ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder.

• DOI: 10.1016/j.ajhg.2017.11.006
• 发表时间: 2017-12-07
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Cuvertino S;Stuart HM;Chandler KE;Roberts NA;Armstrong R;Bernardini L;Bhaskar S;Callewaert B;Clayton-Smith J;Davalillo CH;Deshpande C;Devriendt K;Digilio MC;Dixit A;Edwards M;Friedman JM;Gonzalez-Meneses A;Joss S;Kerr B;Lampe AK;Langlois S;Lennon R;Loget P;Ma DYT;McGowan R;Des Medt M;O'Sullivan J;Odent S;Parker MJ;Pebrel-Richard C;Petit F;Stark Z;Stockler-Ipsiroglu S;Tinschert S;Vasudevan P;Villa O;White SM;Zahir FR;DDD Study;Woolf AS;Banka S
• 通讯作者: Banka S