区域人群3-甲基巴豆酰辅酶A羧化酶缺乏症的筛查、基因检测  

Screening and gene detection of 3-methylcrotonyl-coenzyme A carboxylase deficiency in regional population

作　　者：庄丹燕[1] 张杰[1] 王飞[1] 杨香春 李海波 余颀[1] ZHUANG Dan-yan;ZHANG Jie;WANG Fei;YANG Xiang-chun;LI Hai-bo;YU Qi(Key Laboratory of Comprehensive Prevention and Treatment of Birth Defects,Ningbo Women and Children's Hospital,Zhejiang 315012,China)

机构地区：[1]宁波市妇女儿童医院出生缺陷综合防治重点实验室,浙江315012

出　　处：《中国卫生检验杂志》2023年第4期434-439,共6页Chinese Journal of Health Laboratory Technology

基　　金：浙江省医药卫生科技项目(2023KY1121);宁波市医学重点扶植学科(2022-F26);宁波市公益性科技计划项目(2022S035)。

摘　　要：目的 揭示3-甲基巴豆酰辅酶A羧化酶缺乏症(3-methylcrotonyl-coenzyme A carboxylase deficiency, MCCD)区域新生儿人群发生率、临床特征及基因突变特点。方法 采用串联质谱(tandem mass spectrometry, MS/MS)技术对宁波地区5年间新生儿进行遗传代谢病(inherited metabolic diseases, IMD)筛查,通过尿气相色谱质谱和基因分析对MCCD筛查阳性病例进行临床确诊。结果 2018年-2021年宁波地区新生儿遗传代谢病筛查275 850例,筛出MCCD可疑阳性76例,筛查阳性率为0.28‰。阳性召回后16例选择基因检测,同时行尿液GCMS检测,确诊阳性病例7例,均有筛查指标特征性改变,其中MCCC1和MCCC2基因纯合突变3例,复合杂合突变4例。除此之外,还发现MCCC1和MCCC2基因变异携带7例。MCCC1基因共检测到11个变异,其中3个(c.1377+87C>T,c.1259T>A,c.830G>A)是目前为止未见文献报道的。结论 宁波地区MCCD的发生率约为1/39 407(7/275 850);相关基因变异频率最高的是MCCC1基因的c.1679dup(p.N560Kfs*10),占所有变异的19%(4/21),其次为c.639+2T>A,占14.3%(3/21);发现3个新的MCCC1变异,扩展了MCCC1变异谱。Objective This paper aims to investigate the incidence, clinical characteristics and gene mutation characteristics of 3-methylcrotonyl-coenzyme A carboxylase deficiency(MCCD) in regional neonatal population. Methods Tandem mass spectrometry(MS/MS) was used to screen inherited metabolic diseases(IMD) for five-year neonates in Ningbo area. The MCCD positive cases were confirmed by urine gas chromatography mass spectrometry and gene analysis. Results From 2018 to 2021, 275 850 cases of neonatal genetic metabolic diseases were screened in Ningbo area, and 76 cases were suspected positive for MCCD, with a positive rate of 0.28‰. After recalling of the positive cases, 16 cases were selected for gene testing, and urine GCMS detection was performed at the same time. 7 positive cases were confirmed with characteristic changes of screening indicators, including homozygous mutations of MCCC1 and MCCC2 genes in 3 cases and complex heterozygous mutations in 4 cases. In addition, MCCC1 and MCCC2 gene variants were found in 7 cases. A total of 11 mutations were detected in the MCCC1 gene, of which 3 mutations(c.1377+87C>T, c.1259T>A, c.830G>A) were not reported in the literature so far. Conclusion The incidence rate of MCCD in Ningbo area was 1/39 407(7/275 850). The most frequent variant was c.1679dup(p.n560kfs*10) of MCCC1 gene, accounting for 19%(4/21), followed by c.639+2T>A of MCCC1 gene, accounting for 14.3%(3/21);three new variants of MCCC1 were found, which extended the variation spectrum of MCCC1.

关 键 词：3-甲基巴豆酰辅酶A羧化酶缺乏症 串联质谱技术 新生儿筛查 

分 类 号：R722[医药卫生—儿科]