Prune Belly Syndrome

梅干腹综合症

• 批准号: 9052764
• 负责人: LINDA A. BAKER
• 金额: $ 36.89万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 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/9052764
• 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' s Syndrome; Functional disorder; Gastrostomy; Genes; Genetic; Genetic Counseling; Genomics; Goals; Health; 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; reconstruction; sex; skeletal; targeted treatment; theories; urologic

 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，PBS是一种严重的多系统先天性人类泌尿系统异常。我们将采用个性化医疗方法来确定这种罕见但严重疾病的分子原因。 PBS 的标志性特征包括三联征：1) 腹壁骨骼肌组织发育不全或缺失，2) 膀胱平滑肌发育不良导致尿路扩张伴巨膀胱和反流，3) 双侧睾丸未降。尽管 PBS 很少见且可在产前检测到，但它往往具有毁灭性，20% 的人死产，43% 的人早产，30% 的人在 2 岁时死于肾衰竭或尿脓毒症。 PBS 的男性占主导地位和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 患者在这些基因中不携带基因组变异。因此，其他引起 PBS 的基因仍然未知。我们的研究将利用大量 PBS 先证者和我们招募的多重 PBS 亲属。我们将使用下一代测序来识别引起 PBS 的新基因，并将研究这些基因临床突变的功能影响。我们的具体目标是：1) 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。