Abstract：
BACKGROUND: Hypermethioninemia is an inborn error of metabolism with elevated plasma methionine (Met) caused by methionine adenosyltransferase deficiency. Methionine adenosyltransferase (MAT) I/III deficiency is the most common cause of hypermethioninemia. Except for increased blood Met, most patients have no symptoms, but a small number have nervous system complications, including cognitive impairment and mental retardation.
OBJECTIVE: To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province.
METHODS: 9 cases of hypermethioninemia were screened for amino acids profile and acyl carnitine by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed whole-exome sequencing on 9 families of infants with hypermethioninemia. We identified mutated genes under different models of inheritance and further assessed these mutations through Sanger sequencing and association analysis.
RESULTS: The incidence of neonatal hypermethioninemia was 1:27 228 in Henan province. A total of ten mutations in the MAT1A gene in the 9 patients were identified, including nine reported mutations (c.1070C > T, c.895C > T, c.100 T > A, c.315C > A, c.529C > T, c.623A > C, c.407G > T, c.1066C > T, 867G > T) and one novel mutations (c.772G > C). c.772G > C was detected in 2 families and is the most common variant. 7 infants (7/9) with hypermethioninemia were genetically autosomal dominant, and 2 infants (2/9) with hypermethioninemia were genetically autosomal recessive.
CONCLUSIONS: Our findings expand the mutational spectrum of hypermethioninemia, with the description of one new mutation. They improve the understanding of the genetic background and clinical manifestation of MAT1A in Chinese patients.
OBJECTIVE: To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province.
METHODS: 9 cases of hypermethioninemia were screened for amino acids profile and acyl carnitine by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed whole-exome sequencing on 9 families of infants with hypermethioninemia. We identified mutated genes under different models of inheritance and further assessed these mutations through Sanger sequencing and association analysis.
RESULTS: The incidence of neonatal hypermethioninemia was 1:27 228 in Henan province. A total of ten mutations in the MAT1A gene in the 9 patients were identified, including nine reported mutations (c.1070C > T, c.895C > T, c.100 T > A, c.315C > A, c.529C > T, c.623A > C, c.407G > T, c.1066C > T, 867G > T) and one novel mutations (c.772G > C). c.772G > C was detected in 2 families and is the most common variant. 7 infants (7/9) with hypermethioninemia were genetically autosomal dominant, and 2 infants (2/9) with hypermethioninemia were genetically autosomal recessive.
CONCLUSIONS: Our findings expand the mutational spectrum of hypermethioninemia, with the description of one new mutation. They improve the understanding of the genetic background and clinical manifestation of MAT1A in Chinese patients.
摘要：
背景：高蛋氨酸血症是由甲硫氨酸腺苷转移酶缺乏引起的血浆甲硫氨酸（Met）升高的先天性代谢错误。甲硫氨酸腺苷转移酶（MAT）I/III缺乏是高蛋氨酸血症的最常见原因。除了增加血液Met,大多数患者没有症状，但是少数人有神经系统并发症，包括认知障碍和智力低下。
目的：了解河南省新生儿高蛋氨酸血症患者的基因变异情况。
方法:对245054例新生儿进行氨基酸谱和酰基肉碱串联质谱(MS/MS)检测9例高蛋氨酸血症。我们对9个高蛋氨酸血症婴儿家庭进行了全外显子组测序。我们鉴定了不同遗传模型下的突变基因，并通过Sanger测序和关联分析进一步评估了这些突变。
结果：河南省新生儿高蛋氨酸血症发生率为1:27228。在9例患者中共发现了10个MAT1A基因突变，包括9个报告的突变(c.1070C>T，c.895C>T，c.100T>A，c.315C>A，c.529C>T，c.623A>C，c.407G>T，c.1066C>T，867G>T）和一个新突变（c.772G>C）。c.772G>C在2个家族中检测到，是最常见的变异体。7例（7/9）高蛋氨酸血症的婴儿是遗传常染色体显性遗传，2例（2/9）高蛋氨酸血症婴儿为遗传常染色体隐性遗传。
结论：我们的发现扩展了高蛋氨酸血症的突变谱，描述了一个新的突变。它们提高了中国患者对MAT1A的遗传背景和临床表现的认识。
目的：了解河南省新生儿高蛋氨酸血症患者的基因变异情况。
方法:对245054例新生儿进行氨基酸谱和酰基肉碱串联质谱(MS/MS)检测9例高蛋氨酸血症。我们对9个高蛋氨酸血症婴儿家庭进行了全外显子组测序。我们鉴定了不同遗传模型下的突变基因，并通过Sanger测序和关联分析进一步评估了这些突变。
结果：河南省新生儿高蛋氨酸血症发生率为1:27228。在9例患者中共发现了10个MAT1A基因突变，包括9个报告的突变(c.1070C>T，c.895C>T，c.100T>A，c.315C>A，c.529C>T，c.623A>C，c.407G>T，c.1066C>T，867G>T）和一个新突变（c.772G>C）。c.772G>C在2个家族中检测到，是最常见的变异体。7例（7/9）高蛋氨酸血症的婴儿是遗传常染色体显性遗传，2例（2/9）高蛋氨酸血症婴儿为遗传常染色体隐性遗传。
结论：我们的发现扩展了高蛋氨酸血症的突变谱，描述了一个新的突变。它们提高了中国患者对MAT1A的遗传背景和临床表现的认识。
