Genetic heterogeneity in Rubinstein-Taybi syndrome:: delineation of the phenotype of the first patients carrying mutations in EP300
Genetic heterogeneity in Rubinstein-Taybi syndrome:: delineation of the phenotype of the first patients carrying mutations in EP300
复制标题
DOI：
10.1136/jmg.2006.046698
复制
发表时间：
2007-05-01
影响因子：
4
通讯作者：
Peters, Dorien J. M.
中科院分区：
文献类型：
--
作者：
Bartholdi, Deborah;Roelfsema, Jeroen H.;Peters, Dorien J. M.
背景资料：Rubinstein-Taybi综合征（RSTS）是一种先天性疾病，其特征是生长迟缓，面部畸形，骨骼异常和智力低下。宽拇指和幻觉是这种综合症的特征。RSTS与编码CREB结合蛋白的CREB结合蛋白基因（CREBBP）（也称为CBP）的染色体重排和突变相关。最近，研究表明编码p300蛋白的EP 300突变也会导致RSTS。CBP和EP 300是高度同源的基因，作为全局转录共激活因子发挥着重要作用。目的：报道4例已知的EP 300生殖系突变的RSTS患者的表型。然而，三名患者表现出更温和的骨骼发现的手和脚比通常观察到的患者RSTS.Conclusions：部分的临床变异RSTS的遗传异质性解释。RSTS的诊断必须扩大到包括没有宽拇指或拇的患者。
Background: Rubinstein-Taybi syndrome (RSTS) is a congenital disorder characterised by growth retardation, facial dysmorphisms, skeletal abnormalities and mental retardation. Broad thumbs and halluces are the hallmarks of the syndrome. RSTS is associated with chromosomal rearrangements and mutations in the CREB-binding protein gene (CREBBP), also termed CBP, encoding the CREB-binding protein. Recently, it was shown that mutations in EP300, coding for the p300 protein, also cause RSTS. CBP and EP300 are highly homologous genes, which play important roles as global transcriptional coactivators.Objective: To report the phenotype of the presently known patients with RSTS (n = 4) carrying germline mutations of EP300.Results: The patients with EP300 mutations displayed the typical facial gestalt and malformation pattern compatible with the diagnosis of RSTS. However, three patients exhibited much milder skeletal findings on the hands and feet than typically observed in patients with RSTS.Conclusions: Part of the clinical variability in RSTS is explained by genetic heterogeneity. The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.