先天性肛门直肠畸形合并Townes-Brocks综合征SALL1基因突变的研究  

The study of SALL1 gene mutations in patients with Townes-Brocks syndrome

作　　者：张志波[1] 高红[1] 郭俊斌[1] 王练英[1] 

机构地区：[1]中国医科大学附属第二医院小儿外科,沈阳110004

出　　处：《中华小儿外科杂志》2005年第7期354-356,共3页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金资助项目(批准号:30300370);教育部留学回国人员启动基金(教外司留2003[406])

摘　　要：目的探讨先天性肛门直肠畸形合并Townes-Brocks综合征患儿的临床特征及基因型特征。方法回顾2003年初至2004年4月我院新生儿外科收治的首次入院的先天性肛门直肠畸形病例,判断是否合并Townes-Brocks综合征(肛门直肠畸形是否合并拇指及外耳畸形),对于符合诊断的病例,抽调入院时已存血样,提取基因组DNA,应用PCR及基因组测序等方法分析SALL1基因型。结果24例先天性肛门直肠畸形患儿中,4例符合Townes-Brocks综合征的诊断,4例均为男性,均为高位肛门直肠畸形,其中1例合并直肠尿道瘘,均有耳部发育异常,耳位低垂、发育不良、耳前皮赘等,2例合并拇指发育异常,1例左肾位置异常,输尿管积水扩张、开口异位,2例隐睾,没有追溯到家族史。由于其他原因,患儿父母拒绝做听力筛查,所以不能判定这些患儿是否有感觉神经性耳聋,4例患儿均表现为SALL1基因相同位点的突变,其中一个位点为错义突变(1792bpG→C,Gen-Bankaccessionnos.X98833),对应的丝氨酸→苏氨酸,考虑为Townes-Brocks综合征的病因,3个位点为静止突变(1919bpT→C,2240bpT→C,2311bpA→G,GenBankaccessionnos.X98833),相应的氨基酸没有改变,考虑为等位基因的多态性。结论先天性肛门直肠畸形伴发拇指(趾)、耳部等发育畸形时多为Townes-Brocks综合征,对这样的患儿应尽可能做听力筛查,以早发现、早干预耳聋;Townes-Brocks综合征患儿SALL1基因多有突变,这是该综合征的病因。Objective To explore the relationship between clinical characteristics and genotypes of patients with Townes-Brocks syndrome (TBS).Methods We reviewed the records of all patients with anorectal malformations admitted to this hospital from the beginning of 2003 to April of 2004. All data were evaluated according the major criteria for TBS (anorectal, thumb, and ear malformations) to determine if they have TBS. Genomic DNA of patients with TBS were extracted, SALL1 gene was analyzed with PCR and gene sequencing.Results Four cases had the characteristics of TBS according to their clinical presentations. All of them were male and with high anorectal anomaly. All patients had malformed small outer ears, low set ears, preauricular tags etc. Two had malformed thumbs (triphalangeal thumbs, bifid thumbs), 2 had cryptorchidism, 1 with malformed kidneys. No family history was found. No sensorineural hearing loss could be confirmed in this group because their parents refused to take that examination for their children. SALL1 gene mutations were detected in all patients, all mutations were within 2 nd exon, 1 locus of mis-sense mutation (1792bpG→C, GenBank accession nos. X98833),corresponding S→V,which was postulated the cause for TBS; and 3 loci of silent mutation without amino acid alteration (1919bpT→C, 2240bpT→C, 2311bpA→G, GenBank accession nos. X98833), which was thought to be polymorphism of gene.Conclusions SALL1 gene mutations can be found in most cases of TBS, and these mutations may be related to the cause of TBS.

关 键 词：综合征 基因突变 先天性肛门直肠畸形 形合 感觉神经性耳聋 基因组DNA 基因的多态性 发育异常 听力筛查 基因型特征 新生儿外科 2004年 2003年 基因组测序 直肠尿道瘘 肾位置异常 输尿管积水 临床特征 外耳畸形 方法分析 

分 类 号：R726.5[医药卫生—儿科]