Genomic analysis of 9 infants with hypermethioninemia by whole-exome sequencing among in Henan, China

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.To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province.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.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.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.