异戊酸血症基因新发变异蛋白结构预测  

Structural prediction of a novel variant of isovaleric acidemia gene

作　　者：程威[1] 张志蕾 王彦云[1] 洪冬洋 孙云[1] 蒋涛[1] CHENG Wei;ZHANG Zhilei;WANG Yanyun;HONG Dongyang;SUN Yun;JIANG Tao(Genetic Medicine Center,Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University,Nanjing Maternal and Child Health Hospital,Nanjing,Jiangsu 210004,China)

机构地区：[1]南京医科大学附属妇产医院/南京市妇幼保健院遗传医学中心,江苏南京210004

出　　处：《中国优生与遗传杂志》2023年第6期1208-1212,共5页Chinese Journal of Birth Health & Heredity

基　　金：2021年度南京医科大学科技发展基金项目(NMUB 20210121)。

摘　　要：目的探索异戊酸血症的临床及致病基因突变特点。方法收集1例异戊酸血症的临床资料及提取患儿及父母外周血基因组DNA,采用基于高通量测序技术的基因Panel进行诊断;同时收集国内已经报道的异戊酸血症的临床资料进行汇总,分析其临床表型和基因特点。结果本例患儿串联质谱检测结果显示:异戊酰基肉碱初筛值为0.61μmol/L(正常参考值:0.04~0.35μmol/L),召回复查值为0.55μmol/L,尿气相色谱质谱分析:异戊酰甘氨酸含量为0.62 mmol/mol肌酐,略高于正常值。随访至2岁龄无症状,基因诊断结果示IVD:c.149G>C/c.233G>A。其中c.233G>A未见文献报道,蛋白结构预测该位点可能影响FAD结合效率,导致酶活降低,评估为致病性变异。结论异戊酸血症临床表现无特异性,早期可无症状。新生儿串联质谱筛查有助于该病的早期诊断。Objective To study the clinical and pathogenic gene mutation characteristics of a asymptomatic isovaleric acidemia we found.Methods We gleaned the clinical information of this isovaleric acidemia and collected the peripheral blood of the child and his parents to extract genomic DNA for diagnosis by gene panel based on high-throughput sequencing technology.Meanwhile,we summarized the clinical date of isovaleric acidemias who reported in China and analyzed the clinical phenotype and gene characteristics of this disease.Results The results of tandem mass spectrometry in this case showed that the initial screening value of isoamyl carnitine was 0.61μmol/L(normal reference value:0.04~0.35μmol/L),the recall reexamination value was 0.55μmol/L,and isoamyl glycine in urine gas chromatography mass spectrometry analysis was 0.62 mmol/mol creatinine which slightly higher than the normal value.This case was followed-up to 2 years old without any symptoms.In addition,the gene diagnosis results of IVD gene was c.149G>C/c.233G>A,and the latter mutation has not been reported in the literature.The protein structure predicts of c.233G>A showed it may affect the binding efficiency of FAD which will decrease the enzyme activity.Therefore,it is evaluated as a pathogenic variation.Conclusion The clinical manifestation of isovaleric acidemia is not specific,and it can be asymptomatic in the early phase.Tandem mass spectrometry is helpful for the early diagnosis of the disease.

关 键 词：新生儿筛查 异戊酸血症 早期确诊 基因检测 

分 类 号：R725.8[医药卫生—儿科]