Clinical Phenotype of Imprinted Genes of Chromosome 14

14号染色体印记基因的临床表型

• 批准号: 6360010
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/6360010
• 关键词: biopsy; blood chemistry; body physical characteristic; chromosome aberrations; chromosome disorders; digital imaging; electrocardiography; family genetics; gene expression; genetic disorder diagnosis; genetic screening; genomic imprinting; health education; human subject; information dissemination; intelligence; intelligence tests; laryngoscopy; magnetic resonance imaging; patient care management; patient oriented research; phenotype; postdoctoral investigator; psychological tests

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.

基于对病例报告的调查，14号染色体的母本和父本单亲二体（UPD）具有不同的和特定的表型。这表明14号染色体上有印记基因。已报告的与母体UPD 14相关的特征包括：张力减退、畸形面部特征、智力低下/发育迟缓、青春期提前、产前和产后生长延迟和高胆固醇血症。已报告的与父亲UPD 14相关的特征包括：小睑裂和其他畸形面部特征、智力迟钝/发育迟缓、喉软化、小胸廓、关节挛缩、短长骨、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表达缺失导致与14号染色体的母本和父本单亲二体性相关的不同和独特的表型特征。为了证明这一假设，已获得当地IRB批准和GCRC支持，以仔细和系统地表征与母体和父体UPD相关的临床特征14。我们将招募母亲和父亲UPD均为14的个体，并将其纳入我们的GCRC方案。研究将包括：临床评价、相关身体特征的数字成像或摄影以及每位患者的成像人体测量学;性别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、甘油三酯和总血浆固醇水平;眼科检查;喉镜检查;超声心动图;完整骨骼调查;智商和发育测试;外周血UPD研究以及成纤维细胞系的建立。我们将比较两组之间以及与一般人群之间的差异，以证明母亲和父亲的UPD 14是具有特定表型的不同遗传疾病。对人类疾病的研究，如安格尔曼，普拉德-威利。Beckwith-Wiedemann综合征和Russell-Silver综合征的发现，使人们对印迹基因的识别和对这些印迹基因的作用有了进一步的了解。到目前为止，还没有系统的表征的表型特征的母亲和父亲的UPD 14。通过对UPD 14的特征进行仔细和系统的表征，我们将检验母亲和父亲UPD 14是不同的和不同的疾病的假设。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。这种表型划分将为理解14号染色体上印记基因的作用和发病机制奠定基础。