New insights into the metabolic and nutritional determinants of severe combined immunodeficiency.
Human mutations in MTHFD1 have recently been identified in patients with severe combined immunodeficiency (SCID). SCID results from inborn errors of metabolism that cause impaired T- and B-cell proliferation and function. One of the most common causes of SCID is adenosine deaminase (ADA) deficiency, which ultimately inhibits DNA synthesis and cell division. MTHFD1 has been shown to translocate to the nucleus during S-phase of the cell cycle; this localization is critical for synthesis of thymidyate (dTMP or the "T" base in DNA) and subsequent progression through the cell cycle and cell proliferation. Identification of MTHFD1 mutations that are associated with SCID highlights the potential importance of adequate dTMP synthesis in the etiology of SCID.
Division of Nutritional Sciences; Cornell University ; Ithaca, NY USA.
Martha S
MS
Field
Division of Nutritional Sciences; Cornell University ; Ithaca, NY USA.
Elena
E
Kamynina
Department of Human Genetics, McGill University; Department of Medical Genetics; McGill University Health Center ; Montreal, Quebec, Canada.
David
D
Watkins
Department of Human Genetics, McGill University; Department of Medical Genetics; McGill University Health Center ; Montreal, Quebec, Canada.
David S
DS
Rosenblatt
Division of Nutritional Sciences; Cornell University; Ithaca, NY USA; Graduate Field of Biochemistry; Molecular and Cell Biology; Cornell University; Ithaca, NY USA.
Patrick J
PJ
Stover
Folate; MTHFD1; homocysteine; severe combined immunodeficiency; thymidylate