Clinical Phenotype of Imprinted Genes of Chromosome 14

根据对病例报告的调查，14号染色体的母系和父系单亲二体(UPD)都有不同和特定的表型。这表明14号染色体上存在印记基因。已报道的与母体UPD 14相关的特征包括：低眼压、面部畸形、智力低下/发育迟缓、青春期早期、产前和出生后生长迟缓和高胆固醇血症。已报告的与父亲的UPD 14相关的特征包括：眼裂畸形和其他畸形面部特征，智力低下/发育迟缓，喉软化，小胸，关节痉挛，短长骨，先天性心脏病和产前发育迟缓。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失导致了与14号染色体母系和父系单亲二体相关的不同和明显的表型特征。为了证实这一假设，当地IRB批准和GCRC支持对母系和父系UPD 14相关的临床特征进行了仔细和系统的表征。我们将招募同时患有母系和父系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、相关身体特征的数字成像或摄影以及每个患者的成像人体测量；性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、甘油三酯和血浆总固醇水平；眼科检查；喉镜检查；超声心动图；完整的骨骼测量；智商和发育测试；外周血UPD研究和成纤维细胞系的建立。我们将对这两组人进行相互比较，并与普通人群进行比较，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，。Beckwith-Wiedemann和Russell-Silver综合征导致了印记基因的识别和对这些印记基因的影响的理解。到目前为止，还没有系统地描述母系和父系UPD 14的表型特征。通过仔细和系统地描述UPD 14的特征，我们将检验母系和父系UPD 14是截然不同的不同疾病的假设。我们将建立表型特征的频率，这将使临床医生能够提供UPD 14的预后信息和治疗指南。这种表型描述将为理解14号染色体印记基因的作用和发病机制奠定基础。

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.