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Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency.
Journal article

Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency.

  • Froese DS Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
  • Huemer M Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
  • Suormala T Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
  • Burda P Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
  • Coelho D Institut National de la Santé et de la Recherche Médicale, Unité 954, Nutrition-Genetics and Environmental Exposure, Medical Faculty and National Center of Inborn Errors of Metabolism, University Hospital Center, Nancy University, Vandoeuvre lès Nancy, France.
  • Guéant JL Institut National de la Santé et de la Recherche Médicale, Unité 954, Nutrition-Genetics and Environmental Exposure, Medical Faculty and National Center of Inborn Errors of Metabolism, University Hospital Center, Nancy University, Vandoeuvre lès Nancy, France.
  • Landolt MA Department of Psychosomatics and Psychiatry, University Children's Hospital Zürich, Zürich, Switzerland.
  • Kožich V Institute of Inherited Metabolic Disorders, First Faculty of Medicine - Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
  • Fowler B Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
  • Baumgartner MR Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
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  • 2016-02-14
Published in:
  • Human mutation. - 2016
MTHFR
genotype-phenotype correlation
homocystinuria
remethylation defects
Age of Onset
Animals
Catalytic Domain
Databases, Genetic
Disease Models, Animal
Homocystinuria
Humans
Infant, Newborn
Methylenetetrahydrofolate Reductase (NADPH2)
Muscle Spasticity
Mutation
Neonatal Screening
Psychotic Disorders
English Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is caused by mutations in the MTHFR gene and results in hyperhomocysteinemia and varying severity of disease, ranging from neonatal lethal to adult onset. Including those described here, 109 MTHFR mutations have been reported in 171 families, consisting of 70 missense mutations, 17 that primarily affect splicing, 11 nonsense mutations, seven small deletions, two no-stop mutations, one small duplication, and one large duplication. Only 36% of mutations recur in unrelated families, indicating that most are "private." The most common mutation is c.1530A>G (numbered from NM_005957.4, p.Lys510 = ) causing a splicing defect, found in 13 families; the most common missense mutation is c.1129C>T (p.Arg377Cys) identified in 10 families. To increase disease understanding, we report enzymatic activity, detected mutations, and clinical onset information (early, <1 year; or late, >1 year) for all published patients available, demonstrating that patients with early onset have less residual enzyme activity than those presenting later. We also review animal models, diagnostic approaches, clinical presentations, and treatment options. This is the first large review of mutations in MTHFR, highlighting the wide spectrum of disease-causing mutations.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/68782
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