Methods and Materials for Identifying Polymorphic Variants, Diagnosing Susceptibilities, and Treating Disease

This invention relates to materials and methods associated with polymorphic variants in two enzymes involved in folate-dependent and one-carbon metabolic pathways important in pregnancy-related complications and neural tube birth defects: MTHFD1 (5,10-methylenetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthase) and methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L). These enzymes are extremely important in the promotion of DNA synthesis, a process that is critical for normal placental and fetal development.

Recently, the inventors have discovered that a MTHFD1 polymorphism is also a maternal genetic risk factor for placental abruption, premature separation of a normally implanted placenta. This polymorphism may also be a risk factor for first and second trimester miscarriages. Diagnostic and therapeutic methods are provided in this invention involving the correlation of polymorphic variants in MTHFD1 and MTHFD1L and other genes with relative susceptibility for various pregnancy-related and other complications such as cancer, cardiovascular disease, developmental anomalies and psychiatric illnesses. Both nutrient status and genetic background are independent yet interacting risk factors for impaired folate metabolism. However, the mechanisms that lead to pathology or the mechanisms whereby folate prevents these disorders are unknown. Therefore, a diagnostic and therapeutic invention of this kind would significantly improve the detection and treatment of disorders associated with folate metabolism.


Lawrence Brody (NHGRI)  ➽ more inventions...

Intellectual Property:
PCT Application No. 11/958,126 filed on 2007-12-17
US Application No. 13/008,528 filed on 2011-01-18

A Parle-McDermott et al. MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae. Am J Med Genet A. 2005 Feb 1;132(4):365-368. PubMed abs
A Parle-McDermott et al. A polymorphism in the MTHFD1 gene increases a mother’s risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod. 2005 Jul;11(7):477-480. PubMed abs
A Parle-McDermott et al. Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet. 2006 Jun;14(6):768-772. PubMed abs
B Kempisty et al. MTHFD 1958G>A and MTR 2756A>G polymorphisms are associated with bipolar disorder and schizophrenia. Psychiatr Genet. 2007 Jun;17(3):177-181. PubMed abs

Collaboration Opportunity:

The National Human Genome Research Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Claire Driscoll at 301-402-2537 or for more information.

Licensing Contact:
Eggerton Campbell, Ph.D.
Phone: 301-402-1648

OTT Reference No: E-149-2005-0
Updated: Jul 1, 2007