摘要
目的旨在从基因水平证实多种羧化酶缺乏症（multiplecarboxylasedeficiency，MCD）的诊断，探讨我国MCD患儿的基因突变情况。方法12例MCD患儿接受基因诊断。采用PCR及直接测序法分别对4例生物素酶（biotinidase，BT）缺乏症和8例全羧化酶合成酶（holocarboxylasesynthetas，HLCS）缺乏症进行BT基因和HLCS基因突变分析，对基因新突变通过限制性片段长度多态性分析及患儿父母和50名正常对照者基因检测以证实。结果12例患儿基因突变检出率100％。4例BT缺乏症中发现BT基因突变6种：C．98104del7ins3，C．1369G〉A（V457M），C．1157G〉A（W386X），C．1284C〉A（Y428X），C．1384delA，c-493—1494insT，后4种为新突变。8例HLCS缺乏症中发现HLCS基因突变4种：c．126G〉T（E42D）,c．1994G〉C（R665P），c．1088T〉A（V363D），c．1522C〉T（RS08W），后两种为热点突变[75％（12／16）]，c．1994G〉C为新突变。结论本研究从基因水平上证实了12例MCD的诊断。共发现了6种BT基因突变，4种HLCS基因突变，其中5种为新突变；得出2种HLCS基因的热点突变。
Objective To confirm the diagnosis of multiple carboxylase deficiency （MCD） on the gene level and explore the mutations in Chinese children with MCD. Methods Biotinidase （BT） and holocarboxylase synthetase （HLCS） genes were analyzed by PCR and direct sequencing for the 4 BT deficiency patients and 8 HLCS deficiency patients, respectively. The identified mutations in the parents of the patients and 50 normal controls were screened by PCR restriction fragment length polymorphism and direct DNA sequencing. Results Total detection rate of gene mutation is 100% in the 12 children with MCD. Six mutations were detected in the 4 children with BT deficiency, they were c. 98-104de17ins3, c. 1369G〉A （V457M）, c. 1157G〉A（W386X）, c. 1284C〉A（Y428X）, c. 1384delA and c. 1493_1494insT. The last four were novel mutations. Four mutations were found in the 8 children with HLCS deficiency. They were c. 126G〉T （E42D）,e. 1994G〉C （R665P）, c. 1088T〉A （V363D and c. 1522C〉T （R508W）. The last two were ＂hot spot＂ mutations [ 75 % （ 12/16 ） ], and c. 1994G〉 C （ R665 P） was a novel mutation. Conclusion This study confirmed the diagnosis of 12 patients with MCD on the gene level. Six mutations were found in the BT gene and 4 in the HLCS gene, including 5 novel mutations. Two mutations of the HLCS gene are probably ＂hot spot＂ mutations in Chinese children with HLCS deficiency.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2009年第5期504-510,共7页
Chinese Journal of Medical Genetics
基金
基金项目：国家高技术研究发展计划（863计划）（2007AA022447）
“十一五”国家科技支撑计划支撑项目（2006BA105A05,2006BA105A07）
上海交通大学医学院科技基金（06xJ21024）
关键词
生物素酶
全羧化酶合成酶
串联质谱
突变
多种羧化酶缺乏症
biotinidase
holocarboxylase
tandem mass spectrometry
mutation
multiple carboxylase deficiency
