六个Lowe综合征家系七例患儿的临床特征与OCRL1基因突变  

Clinical features of Lowe syndrome and OCRL1 mutations in seven cases from six families

作　　者：张晓滢 孙良忠 刘婷[2] 李敏[1] 林宏容 岳智慧[3] 陈华木 胡妙月 Zhang Xiaoying;Sun Liangzhong;Liu Ting;Li Min;Lin Hongrong;Yue Zhihui;Chen Huamu;Hu Miaoyue(Department of Pediatrics,Nanfang Hospital of Southern Medical University,Guangzhou 510515,China;Department of Pediatrics,Longgang Central Hospital of Shenzhen,Shenzhen 518000,China;Department of Pediatrics,the First Affiliated Hospital,Sun Yat⁃sen University,Guangzhou 510080,China)

机构地区：[1]南方医科大学南方医院儿科,广州510515 [2]深圳市龙岗中心医院儿科,深圳518000 [3]中山大学附属第一医院儿科,广州510080

出　　处：《中华肾脏病杂志》2020年第5期372-378,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金面上项目(81670610、81470913)。

摘　　要：目的探讨Lowe综合征临床特征、OCRL1基因突变及其与临床表型的关系。方法收集2009年1月至2019年1月就诊于南方医科大学南方医院(4例)和中山大学附属第一医院(3例)Lowe综合征患儿临床资料和外周血标本,提取基因组DNA进行OCRL1基因突变检测。总结分析患儿临床表现特征及OCRL1基因突变与临床表型的关系。结果共收集6个家系7例Lowe综合征患儿临床资料,7例患儿均有眼⁃脑⁃肾表现。其中5个家系6例患儿有先天性白内障和出生时肌张力减低,4例患儿伴眼球震颤,2例有先天性青光眼;另1个家系1例患儿无白内障,仅表现为晶状体变薄。6个家系患儿均有智力运动发育迟缓;有低分子量蛋白尿等近端肾小管功能障碍症状;血清肌酶(AST、LDH、CK、CK⁃MB)升高。6例患儿检测到OCRL1突变,分别位于第10、13、16、18、22、23外显子,其中3个为新突变(c.891G>T、c.1682_1683insAA、c.2564_2567del)。结论本组病例OCRL1新突变比例较高,临床表现存在异质性。第10号外显子突变的患儿临床表现较轻,可无先天性白内障,临床罕见。Objective To explore the characteristics of Lowe syndrome,as well as OCRL1 gene mutation and its relationship with phenotype.Methods Children diagnosed with Lowe syndrome during their visit to Nanfang Hospital of Southern Medical University(4 cases)and the First Affiliated Hospital of Sun Yat⁃sen University(3 cases)from January 2009 to January 2019 were included.The clinical data and peripheral blood samples were collected,and the sequence analysis of OCRL1 was performed after genomic DNA extraction.Then the clinical features of the children and the relationship between OCRL1 mutation and clinical phenotype were analyzed.Results Seven patients from 6 families who presented with Lowe syndrome were included.All of them had different degrees of ocular⁃neural⁃renal symptoms.Six cases from 5 families had congenital cataract and neonatal hypotonia,one case from another family only had a thin lens without cataract.Four cases had nystagmus and 2 cases had glaucoma.Six cases from 6 families had psychomotor retardation and had transaminase(AST),lactate dehydrogenase(LDH),creatine kinase(CK)and creatine kinase⁃MB(CK⁃MB)were increased in all 6 patients who were tested.Mutations of OCRL1 were detected in all the 6 families,which located in exon 10,13,16,18,22 and 23 respectively.The mutations of c.891 G>T,c.1682_1683insAA and c.2564_2567del are novel.Conclusions Three OCRL1 novel mutations in 6 Chinese Lowe syndrome families are identified.The clinical manifestations in different mutations of OCRL1 are heterogeneous.The mutations of c.891 G>T in exon 10 without congenital cataract is rare in clinical.

关 键 词：眼脑肾综合征 DNA突变分析 表型 OCRL1基因 

分 类 号：R72[医药卫生—儿科]