中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2014年
9期
673-677
,共5页
张江伟%王长燕%李明%邱正庆
張江偉%王長燕%李明%邱正慶
장강위%왕장연%리명%구정경
Rubinstein-Taybi综合征%遗传性%基因,显性%CREB结合蛋白
Rubinstein-Taybi綜閤徵%遺傳性%基因,顯性%CREB結閤蛋白
Rubinstein-Taybi종합정%유전성%기인,현성%CREB결합단백
Rubinstein-Taybi syndrome%Hereditary%Gene,dominant%CREB-binding protein
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.
目的 探討Rubinstein-Taybi綜閤徵的臨床及遺傳學特點.方法 對2013年3月至4月北京協和醫院兒科臨床診斷為Rubinstein-Taybi綜閤徵的2例患兒,分析其臨床特徵,採用二代測序技術,進行CREBBP和EP300基因分析,再經Sanger測序對突變進行驗證.結果 2例患兒身高分彆是60 cm、99 cm,低于同年齡同性彆正常兒童身高第3百分位,均有髮際低,頭髮和眉毛濃密,睫毛長,雙眼內眥贅皮和高眉弓等,且拇指和第一腳趾寬而扁,例2伴有語言髮育落後等.在例1檢測到1箇位于CREBBP基因上的錯義突變:c.3535A＞G,p.Ser1179Gly;在例2檢測到1箇同樣位于CREBBP基因上的微缺失突變c.4995_4999delCGCCT,p.Ala1666Pro fs66x.檢測到的2箇突變均為首次報道,缺失突變的緻病性明確;檢測到的錯義突變,根據氨基痠的保守性、公共數據庫資料和患兒典型臨床錶現,推測其為緻病突變.結論 Rubinstein-Taybi綜閤徵主要錶現為生長髮育落後,特殊的麵容及指、趾畸形;CREBBP為緻病基因之一,檢測到該基因突變可以在基因水平確診Rubinstein-Taybi綜閤徵.
목적 탐토Rubinstein-Taybi종합정적림상급유전학특점.방법 대2013년3월지4월북경협화의원인과림상진단위Rubinstein-Taybi종합정적2례환인,분석기림상특정,채용이대측서기술,진행CREBBP화EP300기인분석,재경Sanger측서대돌변진행험증.결과 2례환인신고분별시60 cm、99 cm,저우동년령동성별정상인동신고제3백분위,균유발제저,두발화미모농밀,첩모장,쌍안내자췌피화고미궁등,차무지화제일각지관이편,례2반유어언발육락후등.재례1검측도1개위우CREBBP기인상적착의돌변:c.3535A＞G,p.Ser1179Gly;재례2검측도1개동양위우CREBBP기인상적미결실돌변c.4995_4999delCGCCT,p.Ala1666Pro fs66x.검측도적2개돌변균위수차보도,결실돌변적치병성명학;검측도적착의돌변,근거안기산적보수성、공공수거고자료화환인전형림상표현,추측기위치병돌변.결론 Rubinstein-Taybi종합정주요표현위생장발육락후,특수적면용급지、지기형;CREBBP위치병기인지일,검측도해기인돌변가이재기인수평학진Rubinstein-Taybi종합정.
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.
