Prune Belly Syndrome

梅干腹综合症

基本信息

批准号：
8863944
负责人：
LINDA A. BAKER
金额：
$ 36.83万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8863944
关键词：
2 year old 5 year old Affect Age Amniotic Fluid Appearance Autopsy Bilateral Bladder Candidate Disease Gene Child Clinical Cognition Complex Constipation Cosmetics Cryptorchidism Cystostomy Detection Disease Dysplasia Family Froehlich&apos s Syndrome Functional disorder Gastrostomy Genes Genetic Genetic Counseling Genomics Goals Hospitals Human Infection Kidney Kidney Failure Kidney Transplantation Knowledge Life Link Lower urinary tract Lung Medical Molecular Molecular Profiling Morbidity - disease rate Muscle Muscle Development Mutation Operative Surgical Procedures Organ Organogenesis Pathology Patients Pharmacotherapy Plant Roots Prenatal Diagnosis Quality of life Recruitment Activity Reflux Respiratory System Respiratory physiology Respiratory tract structure Role Severities Signal Pathway Skeletal Muscle Smooth Muscle Specimen Survivors System Technology Testing Testis Therapeutic Intervention Tracheostomy Tube Triad Acrylic Resin Tube Ureter Urethra Urinary tract Urine Urologic Diseases Variant Vesico-Ureteral Reflux abdominal wall base cohort congenital anomaly cost disability fetal filamin genetic variant infancy kindred lung development male next generation sequencing novel outcome forecast personalized medicine premature prenatal pressure proband psychologic public health relevance reconstruction sex skeletal theories urologic

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to expand the knowledge on the genetic basis and molecular mechanisms of Prune Belly Syndrome (PBS), a severe multi-system congenital human urologic anomaly. We will take a personalized medicine approach to identifying the molecular cause of this rare but severe disorder. The hallmark features of PBS include the triad of: 1) hypoplastic or absent abdominal wall skeletal musculature, 2) bladder smooth muscle dysplasia leading to urinary tract dilation with megacystis and refluxing, and 3) bilateral undescended testes. Despite its rarity and prenatal detection, PBS is often devastating, with 20% stillborn, 43% born premature, and 30% dying of renal failure or urosepsis by age 2 years. Male predominance and familial cases of PBS support a sex-limited autosomal recessive or X-linked inheritance. Recently, several genes have been implicated in PBS, but the overwhelming majority of PBS patients do not carry genomic variants in these genes. Thus, additional PBS-causing genes remain unknown. Our study will take advantage of a large cohort of PBS probands and the multiplex PBS kindreds we have recruited. We will use next generation sequencing to identify novel genes causing PBS, and we will study the functional impact of clinical mutations in these genes. Our specific aims are to: 1) identify novel causal genomic variants for PBS, 2) characterize the molecular signature of PBS affected organs, and 3) characterize the role of our recently identified PBS candidate gene.

描述（由申请人提供）：该项目的总体目标是扩大对梅干腹综合症（PBS）的遗传基础和分子机制的了解，这是一种严重的多系统先天性人类泌尿系统异常。我们将采取个性化医疗方法。 PBS 的标志性特征包括三联征：1) 腹壁骨骼肌肉发育不良或缺失，2) 膀胱平滑肌。发育不良导致尿路扩张伴巨囊肿和反流，以及 3) 双侧睾丸未降尽管 PBS 很少见且可在产前检测到，但 PBS 往往具有毁灭性，20% 死产，43% 早产，30% 死于肾衰竭或尿脓毒症。 2 岁以下男性占多数，且 PBS 家族病例支持性别限制的常染色体隐性遗传或 X 连锁遗传。最近，一些基因与 PBS 相关，但绝大多数 PBS 患者不携带这些基因的基因组变异，因此，我们的研究将利用大量 PBS 先证者。我们将使用下一代测序来识别新的 PBS 致病基因，并且我们将研究这些基因的临床突变的功能影响。识别 PBS 的新因果基因组变异，2) 表征 PBS 受影响器官的分子特征，3) 表征我们最近识别的 PBS 候选基因的作用。