母源性3-甲基巴豆酰辅酶A羧化酶缺乏症临床及基因突变分析-论文.pdf

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1、中华医学遗传学杂志2013年lO月第3O卷第5期ChinJMedGenet，October2013，Vo1．30，No．5·临床遗传学论著·母源性3一甲基巴豆酰辅酶A羧化酶缺乏症临床及基因突变分析宫丽霏叶军韩连书邱文娟张惠文高晓岚金晶许浩顾学范【摘要】目的报告5例母源性3一甲基巴豆酰辅酶A羧化酶缺乏症(maternal3-methylcrot0nyl—eoenzymeAearboxylasedeficiency，MCCD)，通过基因突变分析证实其I临床诊断。方法将串联质谱新生儿筛查发现3一羟基异戊酰肉碱(C5一OH)增高的5例新生儿及其母亲纳入研究。用尿气相色谱质谱分析进行MCCDI床诊断

2、；基因突变检测及功能分析明确诊断。结果(1)发现5例无症状母亲血C5一OH浓度明显增高，尿3一羟基异戊酸、3一甲基巴豆酰甘氨酸增高，诊断为良性MCCD。其新生儿血C5一OH浓度增高，3例随访后浓度逐步下降或达正常。(2)发现4种MCCC1基因新变异：e．insl680A(25)、c．203C~>T(P．A68V)、c．572T>C(P．1．191P)、c．639+5G>T和2种MCCC2基因突变c．1406G>T(P．R469I，新变异)及c．592C~>T(P．Q198X)。新变异可能影响蛋白结构和功能。结论对筛查血C5一OH增高的新生儿母亲应常规检测以诊断母源性MCCD。MCCC1基因

3、突变多见。【关键词】3一甲基巴豆酰辅酶A羧化酶缺乏症；3一甲基巴豆酰辅酶A羧化酶；基因突变；质谱分析Clinicalandmutationalfeaturesofmaternal3-methylcrotonyl-coenzymedeficiencyGONGLi—fei，YEJun，HANLian—shu，QJUWenJuan，ZHANGHui—wen，GA0Xiao—lan，JINJing，XUHaG，GUXue—Jan．(DepartmentofPediatricEd0f”oZ0gandGeneticMetabolism，ShanghaiInstituteforPediatricRese

4、ar~h，XinhuaHospital，ShanghaiJiaotongUniversitySchooloJMedicine，Shanghai200092，P．R．China)C0rr0”gauthor：YEJun，Email：yejun2314(ahoo．corn．cn[Abstract1ObjectiveToreporton5patientswithmaternal3-methyIcrotonyl—coenzymeAcarboxylasedeficiency(MCCD)andtoconfirmtheclinicaldiagnosisthroughmutationanalysis．Met

5、hodsFiveneonateswithhigherblood3-hydroxy—isovalery1carnitine(C5一OH)concentrationdetecteduponnewbornscreeningwithtandemmassspectrometryandtheirmotherswererecruited．Urinaryorganicacidswereanalyzedwithgaschromatographymassspectrometry．GenemutationandproteinfunctionanalysiswereperformedbyPCR—directseq

6、uencingandPolyPhen一2software．ResultsHigherbloodC5OHconcentrations(5．1121．77／~mol／I)andabnormal3-hydroxyisovalerateand3-methylcrotony1一glycineinurineweredetectedinthefiveasymptomaticmothers，whowerediagnosedasbenignMCCD．HigherC5一OHconcentrationwasalsodetectedintheirneonatesbytandemmassspectrometry，w

7、hichhadgraduallydecreasedtonormallevelsinthreeneonates．Fournewvariations，i．e．，c．ins1680A(25)，c．203C~>T(P．A68V)，c．572T>C(P．I191P)andc．639+5G>TweredetectedintheMCCC1gene。inadditionwith2mutationsEe．1406G~>T(P．R469I，