瓜氨酸血症患儿ASS1、ASL和SLC25A13基因的突变分析  

Genetic analysis of ASSI , ASL and SLC25A13 in citrullinemia patients

作　　者：温鹏强[1] 陈占玲[2] 王国兵[1] 刘晓红[3] 陈黎[4] 陈淑丽[4] 万力生[5] 崔冬[1] 赏月[3] 李成荣[1] 

机构地区：[1]广东省深圳市儿童医院儿科研究所,518026 [2]东莞市人民医院内分泌科 [3]广东省深圳市儿童医院新生儿科,518026 [4]广东省深圳市儿童医院神经内科,518026 [5]广东省深圳市儿童医院中医科,518026

出　　处：《中华医学遗传学杂志》2014年第3期268-271,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81102227）;深圳市医学重点学科专项经费（2001B18、2001819）;深圳市科技计划项目（医疗卫生类）重点项日（201201005）;深圳市科技计划项目（医疗卫生类）一般项目（201302107,201102068）;广东省医学科研基金（A2012582、A2013604）;深圳市科技研发资金项目（JCYJ20130401114111449）;东莞市医疗卫生科技计划一般项目（20131051010102）;南京中医药大学中医学优势学科开放课题（Y$2012ZYX212）

摘　　要：目的探讨4例瓜氨酸血症患者相关致病基因突变类型。方法提取4例患儿血基因组DNA标本，针对可引起瓜氨酸血症候选基因ASS1、ASL、SLC25A13，应用PCR技术扩增包括外显子及其侧翼区在内的DNA序列。扩增产物直接测序，确定基因突变类型。结果1例患儿为精氨酸琥珀酸合成酶缺乏症，为ASSl基因C．236C〉T（P．$79F）与C．431C〉G（P．P144R）双重杂合突变；两例患儿为精氨酰琥珀酸尿症，分别为ASL基因C．434A〉G（P．D145G）与C．1366C〉T（P．R456W），C．331C〉T（P．R111W）与IVS8＋2insT双重杂合突变；另一例1岁患儿发现携带有SLC25A13基因85ldel4杂合突变，诊断为成年型瓜氨酸血症Ⅱ型。结论通过相关致病基因分析，准确地确定了4例患儿的疾病类型。Objective To detect potential mutations of ASS1, ASL and SLC25A13 genes in four patients manifesting citrullinemia. Methods Genomic DNA was extracted from peripheral blood leukocytes. Exons and their flanking sequences of the three genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing. Results Based on DNA sequence analysis, one case was diagnosed with argininosuccinate synthetase deficiency, and the mutation type （ASS1 gene） was c. 236C〉T （p. $79F） ＋ c. 431C〉G （p. P144R）. Two cases were diagnosed with argininosuccinic aciduria （ASL gene）, and their gene mutations were c. 434A〉G （p. D145G） ＋ c. 1366C〉T （p. R456W） and c. 331C〉T （p. RlllW） ＋ IVS8＋2insT, respectively. A thirteen months boy who carried a heterozygous 851del4 mutation （SLC25A13 gene） was diagnosed with citrullinemia adult-onset type II. Conclusion Through analysis of relevant pathogenic genes, four patients have been diagnosed.

关 键 词：瓜氨酸血症 精氨酸琥珀酸合成酶缺乏症 精氨酰琥珀酸尿症 ASS1基因 ASL基因 SLC25A13基因 成年型瓜氨酸血症Ⅱ型 遗传代谢病 

分 类 号：R725.8[医药卫生—儿科]