Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia

Muriello, Michael; Viall, Sarah; Cusmano‐Ozog, Kristina; Ferreira, Carlos R.

doi:10.1016/j.ymgmr.2017.07.004

Cited by 8 publications

(6 citation statements)

References 27 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study reported a prevalence of 1/30,893 in Suzhou population of newborns. Of 13 Suzhou hypermethioninemia patients, 10 cases carried the dominant mutation c.791G > A (Pérez Mato et al, 2001; Muriello et al, 2017). Previous studies reported that the c.791G > A was the most prevalent mutation in Asian populations, such as Japanese, Chinese in Taiwan, and so on (Chien et al, 2005; Nagao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…MATA1 deficiency is inherited either as autosomal-recessive or autosomal-dominant. Most MAT1A mutations give rise to autosomal recessive phenotypes, but several autosomal dominant mutations have also been observed, including c.776C > T, c.791G > A (Muriello et al, 2017), c.746G > A, and c.838G > A (Kim et al, 2016). With the exception of a few individuals with hypermethioninemia who present with abnormal neurological symptoms, most patients generally are free of major clinical manifestation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population

Wang

Zhang

et al. 2019

Front. Genet.

View full text Add to dashboard Cite

Expanded newborn screening for inborn errors of metabolism (IEMs) by tandem mass spectrometry (MS/MS) could simultaneously analyze more than 40 metabolites and identify about 50 kinds of IEMs. Next generation sequencing (NGS) targeting hundreds of IMEs-associated genes as a follow-up test in expanded newborn screening has been used for genetic analysis of patients. The spectrum, prevalence, and genetic characteristic of IEMs vary dramatically in different populations. To determine the spectrum, prevalence, and gene mutations of IEMs in newborns in Suzhou, China, 401,660 newborns were screened by MS/MS and 138 patients were referred to genetic analysis by NGS. The spectrum of 22 IEMs were observed in Suzhou population of newborns, and the overall incidence (excluding short chain acyl-CoA dehydrogenase deficiency (SCADD) and 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD)) was 1/3,163. The prevalence of each IEM ranged from 1/401,660 to 1/19,128, while phenylketonuria (PKU) (1/19,128) and Mild hyperphenylalaninemia (M-HPA) (1/19,128) were the most common IEMs, followed by primary carnitine uptake defect (PCUD) (1/26,777), SCADD (1/28,690), hypermethioninemia (H-MET) (1/30,893), 3-MCCD (1/33,412) and methylmalonic acidemia (MMA) (1/40,166). Moreover, 89 reported mutations and 51 novel mutations in 25 IMEs-associated genes were detected in 138 patients with one of 22 IEMs. Some hotspot mutations were observed for ten IEMs, including PAH gene c.728G > A, c.611A > G, and c.721C > T for Phenylketonuria, PAH gene c.158G > A, c.1238G > C, c.728G > A, and c.1315+6T > A for M-HPA, SLC22A5 gene c.1400C > G, c.51C > G, and c.760C > T for PCUD, ACADS gene c.1031A > G, c.164C > T, and c.1130C > T for SCAD deficiency, MAT1A gene c.791G > A for H-MET, MCCC1 gene c.639+2T > A and c.863A > G for 3-MCCD, MMUT gene c.1663G > A for MMA, SLC25A13 gene c.IVS16ins3Kb and c.852_855delTATG for cittrullinemia II, PTS gene c.259C > T and c.166G > A for Tetrahydrobiopterin deficiency, and ACAD8 gene c.1000C > T and c.286C > A for Isobutyryl coa dehydrogenase deficiency. All these hotspot mutations were reported to be pathogenic or likely pathogenic, except a novel mutation of ACAD8 gene c.286C > A. These mutational hotspots could be potential candidates for gene screening and these novel mutations expanded the mutational spectrum of IEMs. Therefore, our findings could be of value for genetic counseling and genetic diagnosis of IEMs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population

Wang

Zhang

et al. 2019

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…This is a pathological condition caused by excessive consumption of Met, due to supplementation or a high protein diet, liver disease, premature birth, or can occur in case of an innate metabolism error, when Met is not properly metabolized [16]. Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by an impairment of enzymes such as Methionine adenosyltransferase (MAT) [17], glycine Nmethyltransferase (GNMT) [18], and S-adenosylhomocysteine hydrolase (AHCY) [19]. Despite that, hypermethioninemia can occur due to a secondary metabolic disorder like homocystinuria induced by cystathionine betasynthase (CBS) deficiency [20], tyrosinemia type I with mutations in the fumarylacetoacetate hydrolase (FAH) gene [21], and citrin deficiency [22].…”

Section: Introductionmentioning

confidence: 99%

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

et al. 2020

View full text Add to dashboard Cite

Methionine (Met) has important functions for homeostasis of various species, including zebrafish. However, the increased levels of this amino acid in plasma, a condition known as hypermethioninemia, can lead to cell alterations. Met is crucial for the methylation process and its excesses interfere with the cell cycle, an effect that persists even after the removal of this amino acid. Some conditions may lead to a transient increase of this amino acid with unexplored persistent effects of Met exposure. In the present study, we investigated the behavioral and neurochemical effects after the withdrawal of Met exposure. Zebrafish were divided into two groups: control and Met-treated group (3 mM) for 7 days and after maintained for 8 days in tanks containing only water. In the eighth day post-exposure, we evaluated locomotion, anxiety, aggression, social interaction, and memory, as well as oxidative stress parameters, amino acid, and neurotransmitter levels in the zebrafish brain. Our results showed that 8 days after Met exposure, the treated group showed decreased locomotion and aggressive responses, as well as impaired aversive memory. The Met withdrawal did not change thiobarbituric acid reactive substances, reactive oxygen species, and nitrite levels; however, we observed a decrease in antioxidant enzymes superoxide dismutase, catalase, and total thiols. Epinephrine and cysteine levels were decreased after the Met withdrawal whereas carnitine and creatine levels were elevated. Our findings indicate that a transient increase in Met causes persistent neurotoxicity, observed by behavioral and cognitive changes after Met withdrawal and that the mechanisms underlying these effects are related to changes in antioxidant system, amino acid, and neurotransmitter levels.

show abstract

“…Myelination disorder was reported when Arg292Cys mutation was paired with Arg356Leu or with Glu145Lys [10,11,40]. The positions of some of the substituted amino acids in protein structure might explain the alterations of enzyme activity [45][46][47]. Mutations at Arg356 (Arg356Pro, Arg356Leu, and Arg356Gln) showed great influence in Japanese patients, and substitutions at this residue can be clinically informative for molecular diagnosis [40].…”

Section: Mutations In the Mat1a Gene And Genotype-phenotype Correlationmentioning

confidence: 99%

Diagnostic Value of the MAT1A Gene Mutations in Methionine Adenosyltransferase I/III Deficiency: Possible Relevance to Various Neurological Manifestations

Furujo¹,

Kubo²,

Kinoshita³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

Methionine adenosyltransferase I/III (MAT I/III) deficiency is a metabolic disorder exhibiting persistent hypermethioninemia and neurological problems such as mental retardation and movement disorders by brain demyelination. Current diagnosis of MAT I/III deficiency completely depends upon newborn mass screening. Recently, correlation between the type of mutation of the MAT1A gene and clinical presentation has been investigated. The most common mutation, heterozygous for the autosomal dominant Arg264His mutation, is a relatively benign phenotype which requires no treatment. In contrast, care must be taken on the Arg292Cis mutation, especially if compounded with mutations at Arg356 (Arg356Pro, Arg356Leu, and Arg356Gln), for association of myelination disorder. Since MAT I/III catalyzes conversion of methionine to produce S-adenosylmethionine (SAM), supplementation of SAM is a therapeutic strategy to improve neurological problems. Hypermethioninemia can be corrected by methionine restriction; however, it may cause depletion of SAM. DNA testing is important for early diagnosis to prevent neurological manifestations.

show abstract

Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia

Cited by 8 publications

References 27 publications

Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population

Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

Diagnostic Value of the MAT1A Gene Mutations in Methionine Adenosyltransferase I/III Deficiency: Possible Relevance to Various Neurological Manifestations

Contact Info

Product

Resources

About