CREBBP基因突变所致Rubinstein-Taybi综合征二例临床和遗传学特征

CREBBP gene mutation in two boys with Rubinstein-Taybi syndrome

目的 探讨Rubinstein-Taybi综合征的临床及遗传学特点.方法 对2013年3月至4月北京协和医院儿科临床诊断为Rubinstein-Taybi综合征的2例患儿,分析其临床特征,采用二代测序技术,进行CREBBP和EP300基因分析,再经Sanger测序对突变进行验证.结果 2例患儿身高分别是60 cm、99 cm,低于同年龄同性别正常儿童身高第3百分位,均有发际低,头发和眉毛浓密,睫毛长,双眼内眦赘皮和高眉弓等,且拇指和第一脚趾宽而扁,例2伴有语言发育落后等.在例1检测到1个位于CREBBP基因上的错义突变：c.3535A＞G,p.Ser1179Gly;在例2检测到1个同样位于CREBBP基因上的微缺失突变c.4995_4999delCGCCT,p.Ala1666Pro fs66x.检测到的2个突变均为首次报道,缺失突变的致病性明确;检测到的错义突变,根据氨基酸的保守性、公共数据库资料和患儿典型临床表现,推测其为致病突变.结论 Rubinstein-Taybi综合征主要表现为生长发育落后,特殊的面容及指、趾畸形;CREBBP为致病基因之一,检测到该基因突变可以在基因水平确诊Rubinstein-Taybi综合征.

Objective To investigate the clinical and genetic features of 2 patients with Rubinstein-Taybi syndrome.Method Using next generation sequencing （NGS） the CREBBP and EP300 genes of 2 children who were diagnosed as Rubinstein-Taybi syndrome at Peking Union Medical College Hospital.The mutations identified by NGS were verified by PCR were analyzed.Result The 2 patients at the age of 5 months and 4.5 years manifested short stature （the height were 60 cm and 99 cm respectively）,low hairline,thick and dense hair and eyebrows,long lash,epicanthus of both eyes,protruded supercilliary arch,broad and flat thumbs and halluces,and particular facial abnormalities.Patient 2 had language retardation besides.One missense mutation of c.3535A ＞ G,p.Ser1179Gly was found in CREBBP gene in patient 1 and one microdeletion mutation of c.4995 _4999delCGCCT,p.Ala1666Pro fs66x was found inpatient 2.Both mutations were reported for the first time.Conclusion Rubinstein-Taybi syndrome is characterized by mental and growth retardation,wide and fiat thumbs and first toes,and dysmorphic facial features.CREBBP is one of the causative genes.Mutation detection on CREBBP gene can confirm the diagnosis of Rubinstein-Taybi syndrome.