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: 6638047
• 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/6638047
• 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.

根据病例报告的调查，14号染色体的母亲和父亲的单亲二体（UPD）具有不同的特异性表型。这表明在14号染色体上有印迹基因。已报道的与母体UPD 14相关的特征包括：低张力、面部畸形、智力迟钝/发育迟缓、青春期提前、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：睑下垂和其他畸形面部特征、智力迟钝/发育迟缓、喉软症、小胸、关节挛缩、短长骨、先天性心脏病和产前生长迟缓。我们认为，印迹基因位于14号染色体上，这些印迹基因的过表达或不表达导致了14号染色体母亲和父亲的单亲二体相关的不同和独特的表型特征。为了证明这一假设，已经获得了当地IRB的批准和GCRC的支持，对母亲和父亲的UPD 14相关的临床特征进行了仔细和系统的表征。我们将招募母亲和父亲都患有UPD 14的个体，并将他们纳入我们的GCRC方案。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；性和生长激素水平和垂体功能测试；脑成像研究；血清胆固醇、甘油三酯和血浆总固醇水平；眼科检查;喉镜检查;超声心动图;完整的骨骼调查；智商和发展测试；外周血UPD的研究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，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Angelman， Prader-Willi，。beck - wiedemann综合症和Russell-Silver综合症，已经导致了对印迹基因的识别和对这些印迹基因的影响的理解。迄今为止，还没有系统的表征母亲和父亲的UPD 14的表型特征。通过仔细和系统地描述UPD 14的特征，我们将检验母亲和父亲的UPD 14是不同的疾病的假设。我们将建立表型特征的频率，这将允许临床医生为UPD 14提供预后信息和治疗指南。这种表型描述将为理解14号染色体上印迹基因的作用和发病机制奠定基础。