Cockayne综合征两例临床特征与基因突变分析  

Clinical and molecular analysis of two Chinese siblings with Cockayne syndrome

作　　者：周知子[1] 刘丽[1] 吴莫龄[1] 刘鸿圣[1] 蔡燕娜[1] 盛慧英[1] 李秀珍[1] 程静[1] 李端[1] 黄永兰[1] 

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心遗传与内分泌科,510623

出　　处：《中华儿科杂志》2016年第1期56-60,共5页Chinese Journal of Pediatrics

基　　金：国家科技支撑计划（2012BAI09B04）;广东省自然科学基金（2015A030313770）

摘　　要：目的分析Cockayne综合征患儿临床特征及基因突变。方法分析归纳2013年7月至2014年11月广州妇女儿童医疗中心收治的一对同胞兄弟共患经典型Cockayne综合征的临床特点；提取患儿及其血缘父母外周血全基因组DNA，用PCR方法扩增ERCC6基因全部外显子及与其相连的内含子区，扩增产物行双向测序，查找突变位点。结果患儿为同胞两兄弟，分别为4岁8月龄和7岁5月龄。均因“生长和智力落后数年”就诊，母孕产史均无异常。1岁前，患儿身高、体重均在正常范围内。1岁半后均出现身高、体重增长缓慢，运动发育落后，眼、皮肤光敏感，听力及视神经损害，小头、眼窝深邃。例1（先证者）就诊时身高90．8cm，体重9．1kg，头围41cm，胸围44cm；例2（先证者胞兄）就诊时身高92cm，体重11．2kg，头围41cm，胸围46cm。例1在4岁半，例2在7岁时头颅MRI检查提示全脑萎缩，脑室扩大，髓鞘形成不良。头颅磁共振波谱分析（氢谱）-MR成像提示左右两侧背侧丘脑、岛叶及左侧半卵圆中心神经元损伤。头颅CT提示双侧基底节对称性钙化。ERCC6基因突变分析提示兄弟俩ERCC6基因均存在c．1357C〉T（P．Arg453Ter）与c．1607T〉G（P．Leu536Trp）复合杂合致病突变，突变分别遗传自患儿母亲和父亲。结论Cockayne综合征患儿具有出生时正常，生后逐渐出现生长发育迟缓，语言、智力落后，脑损伤、小头畸形，眼窝深邃，皮肤光敏感等临床特征，存在ERCC6基因突变，易误诊为脑瘫、先天性小头畸形等。Objective Cockayne syndrome is a rare disease and difficult to be recognized. This study aimed to expand the knowledge of the clinical and molecular characteristics of the children with Cockayne syndrome （CS）. Method Clinical data of two siblings with classic CS of Guangzhou Women and Children＇s Medical Center from July 2013 to November 2014 were obtained and analyzed. The whole DNA of peripheral blood was collected from two CS siblings and their parents. Amplification of all exons and adjacent introns for ERCC6 gene was conducted using PCR, and measurement of reaction product was performed to find mutation sites by two-way sequencing. Result Two affected siblings were males, and came from unconsanguineous parents, 7 years and 5 months old and 4 years and 8 months old, respectively. They were in treatment because of developmental and mental retardation for years. When they were younger than one year of age, their heights and weight were within normal limits. However, poor growth of height and weight and psychomotor retardation appeared after one and a half years of age, as well as skin and eye sensitivity to sunshine, hearing impairment, optic nerve atrophy, microeephaly, and deep-set eyes. The proband＇s height was 90. 8 cm, and weight 9. 1 kg, head circumference 41 em, and chest circumference 44 cm when he was taken to hospital. The elder brother of the proband had a height of 92 cm, weight 11.2 kg, head circumference 41 cm, and chest circumference 44 cm when he was taken to hospital. When the proband was four and a half years old, ventricular enlargement, hypomyelination, and brain atrophy were detected for his elder brother at 7 years of age by cranial MRI. MRS imaging indicated that damages occurred at the left and right sides of dorsal Ihalamus, lohus insularis, along with the left half circle of central neurons. Symmetrieal calcificali^m on bilateral basal ganglia was found on Ihe brain CT scan. Pathogenic compound heterozygous c. 1357C 〉 T （p. Arg453Ter） and c. 1607T 〉 G （p. Leu536Trp）

关 键 词：Cockayne综合征 ERCC6 脑萎缩 光过敏疾患 

分 类 号：R725.9[医药卫生—儿科]