Clinical Phenotype of Imprinted Genes of Chromosome 14

14号染色体印记基因的临床表型

基本信息

批准号：
6536394
负责人：
VERNON R SUTTON
金额：
$ 12.1万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2006-06-30
项目状态：
已结题

项目摘要

Based on a survey of case reports both maternal and paternal uniparental disomy (UPD) for chromosome 14 have different and specific phenotypes. This suggests that there are imprinted genes on chromosome 14. Features that have been reported in association with maternal UPD 14 include: Hypotonia, dysmorphic facial features, mental retardation/developmental delay, early puberty, prenatal and postnatal growth delay and hypercholesterolemia. Features that have been reported in association with paternal UPD 14 include: Blepharophimosis and other dysmorphic facial features, mental retardation/developmental delay, laryngomalacia, small thorax, joint contractures, short long bones, congenital heart disease and prenatal growth delay. We believe that imprinted genes are located on chromosome 14 and that overexpression or absence of expression of these imprinted genes causes the different and distinct phenotypic features associated with maternal and paternal uniparental disomy for chromosome 14. In order to prove this hypothesis, local IRB approval and GCRC support has been obtained for careful and systematic characterization of the clinical features associated with both maternal and paternal UPD 14. We will recruit individuals with both maternal and paternal UPD 14 and enroll them in our GCRC protocol. Studies will include: Clinical evaluation, digital imaging or photography of relevant physical features and imaging anthropometrics of each patient; sex and growth hormone levels and pituitary function tests; brain imaging studies; serum cholesterol, triglyceride and total plasma sterol levels; ophthalmologic exam; laryngoscopy; echocardiography; complete skeletal survey; IQ and developmental testing; peripheral blood UPD studies and establishment of a fibroblast cell line. We will compare both groups with one another and with the general population to prove that maternal and paternal UPD 14 are distinct genetic disorders with specific phenotypes. The study of human disorders, such as Angelman, Prader-Willi,. Beckwith-Wiedemann and Russell-Silver syndromes, has led both to the identification of imprinted genes and to an understanding of the effects of those imprinted genes. To date, there has been no systematic characterization of the phenotypic features of maternal and paternal UPD 14. Through careful and systematic characterization of the features of UPD 14 we will test the hypothesis that maternal and paternal UPD 14 are distinct and different disorders. We will establish the frequency of phenotypic features, which will allow clinicians to provide prognostic information and treatment guidelines for UPD 14. This phenotype delineation will lay the foundation for understanding the effects and pathogenesis of imprinted genes on chromosome 14.

根据病例报告调查，14 号染色体的母本单亲二体性 (UPD) 具有不同且特定的表型。这表明 14 号染色体上有印记基因。据报道，与母体 UPD 14 相关的特征包括：张力减退、面部畸形、智力低下/发育迟缓、青春期早期、产前和产后生长迟缓和高胆固醇血症。已报道的与父亲 UPD 14 相关的特征包括：睑裂和其他畸形面部特征、智力低下/发育迟缓、喉软化、胸廓小、关节挛缩、长骨短、先天性心脏病和产前生长迟缓。我们认为印记基因位于 14 号染色体上，这些印记基因的过度表达或缺乏表达会导致与 14 号染色体的母本和父本单亲二体性相关的不同且独特的表型特征。为了证明这一假设，当地 IRB 批准并已获得 GCRC 支持，以仔细、系统地表征与母亲和父亲 UPD 14 相关的临床特征。我们将招募同时患有母亲和父亲 UPD 14 的个体，并将他们纳入我们的 GCRC 协议。研究将包括：临床评估、每位患者相关身体特征的数字成像或摄影以及成像人体测量学；性激素和生长激素水平以及垂体功能测试；脑成像研究；血清胆固醇、甘油三酯和血浆总甾醇水平；眼科检查；喉镜检查；超声心动图；完成骨骼调查；智商和发育测试；外周血UPD研究和成纤维细胞系的建立。我们将对两组人群以及一般人群进行比较，以证明母本 UPD 14 是具有特定表型的不同遗传性疾病。对人类疾病的研究，如Angelman、Prader-Willi等。 Beckwith-Wiedemann 和 Russell-Silver 综合征导致了印记基因的鉴定以及对这些印记基因的影响的理解。迄今为止，还没有对母本 UPD 14 的表型特征进行系统表征。通过对 UPD 14 的特征进行仔细和系统的表征，我们将检验母本和父本 UPD 14 是不同的疾病的假设。我们将确定表型特征的频率，这将使临床医生能够为 UPD 14 提供预后信息和治疗指南。这种表型描述将为了解 14 号染色体上印记基因的影响和发病机制奠定基础。