摘要目的:探讨甲硫氨酸腺苷转移酶Ⅰ/Ⅲ(methionine adenosyltransferase Ⅰ/Ⅲ，MAT Ⅰ/Ⅲ)缺乏症的新生儿筛查及 MAT1A基因变异情况。 方法:应用串联质谱技术对泉州地区364 545份新生儿样本进行遗传代谢病筛查，应用高通量测序技术结合Sanger测序法对MAT Ⅰ/Ⅲ缺乏症患儿的相关致病基因进行检测，寻找可能的致病变异位点。采用MutationTaster和HSF软件对发现的新变异进行致病性分析预测。结果:新生儿筛查检测出3例MAT Ⅰ/Ⅲ缺乏症患儿，发病率为1/121 515。氨基酸和酰基肉碱分析结果显示3例患儿的血甲硫氨酸浓度在筛查和随访期间均有不同程度的升高，随访期间生长发育正常。3例患儿均被检测到 MAT1A基因变异，共发现3种变异类型，包括2种错义变异c.776C>T(p.Ala259Val)、c.791G>A(p.Arg264His)，和1种同义变异c.360C>T(p.Cys120Cys)。 MAT1A基因c.776C>T(p.Ala259Val)和c.791G>A(p.Arg264His)变异为已知的致病变异，c.360C>T(p.Cys120Cys)为尚未见报道的新变异。用MutationTaster和HSF对c.360C>T(p.Cys120Cys)进行预测分析，结果显示变异会引起剪接改变，进而影响蛋白的结构和功能。 结论:本研究较为系统的分析了本地区MAT Ⅰ/Ⅲ缺乏症的新生儿筛查及 MAT1A基因变异情况，阐明了本地区MAT Ⅰ/Ⅲ缺乏症的发病率，发现1个新的 MAT1A基因变异，丰富了 MAT1A基因变异谱，为MAT Ⅰ/Ⅲ缺乏症的诊断提供了依据。

abstractsObjective:To summarize newborn screening for methionine adenosyltransferase Ⅰ/Ⅲ (MAT Ⅰ/Ⅲ) deficiency in Quanzhou region of Fujian Province.Methods:A total of 364 545 neonates were screened for inherited metabolic diseases by tandem mass spectrometry. High-throughput next generation sequencing combined with Sanger sequencing was used to detect potential variants in newborns with MAT Ⅰ/Ⅲ deficiency. Pathogenicity of suspected variants was predicted by using MutationTaster and HSF software.Results:Three newborns were identified with MAT Ⅰ/Ⅲ deficiency by newborn screening, which yielded an incidence rate of 1 in 121 515. Amino acid and acylcarnitine analysis suggested that the serum methionine of the three patients have increased to various extents.All patients showed normal growth and development during follow-up, and were found to carry MAT1A gene variants including two missense variants [c.776C>T (p.Ala259Val) and c. 791G>A (p.Arg264His)] and a synonymous variant [c.360C>T(p.Cys120Cys)]. Among these, c. 776C>T (p.Ala259Val) and c. 791G>A (p.Arg264His) were known to be pathogenic, whereas c. 360C>T (p.Cys120Cys) was a novel variant. Bioinformatics analysis suggested that this variant may alter RNA splicing and affect the structure and function of the MAT1A protein. Conclusion:A systematic review of newborn screening for MAT Ⅰ/Ⅲ deficiency was provided. Discovery of the novel variant has enriched the variant profile of the MAT1A gene and provided a basis for the diagnosis of this disease.