Newborn screening and variant analysis for methionine adenosyltransferase I/III deficiency.
10.3760/cma.j.issn.1003-9406.2020.05.008
- VernacularTitle:甲硫氨酸腺苷转移酶Ⅰ/Ⅲ缺乏症的新生儿筛查及基因变异研究
- Author:
Chunmei LIN
1
;
Quanzhi ZHENG
;
Mengyi JIANG
;
Yiming LIN
Author Information
1. Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Fuzhou, Fujian 362000, China. 9537237@qq.com.
- Publication Type:Case Reports
- MeSH:
Amino Acid Metabolism, Inborn Errors;
diagnosis;
China;
Genetic Variation;
Humans;
Infant, Newborn;
Methionine Adenosyltransferase;
deficiency;
genetics;
Neonatal Screening
- From:
Chinese Journal of Medical Genetics
2020;37(5):527-531
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: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.
