The present invention provides assays for the detection of human RFX4_v3 polymorphisms or deficiencies that may lead to the determination of an individual's risk of developing hydrocephalus.

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States.  Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults.  Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities.  Improved diagnostics are needed for assessing the risks of developing this debilitating disease.

 

The inventors have shown that RFX4_v3, a splice variant of the Regulatory Factor X4 (RFX4) transcription factor, is associated with the development of neurological structures.  The reduction or absence of RFX4_v3 promotes the development of congenital hydrocephalus.  This invention describes RFX4_v3 polypeptides and nucleic acids, as well as methods for detection of RFX4_v3 polymorphisms associated with congenital hydrocephalus.  Also described are treatment methods including the RFX4_v3 polypeptide and RFX4_v3 transgenic animals and antibodies.

 

Applications:

·     Prenatal diagnostic assay for identifying children at risk for congenital hydrocephalus

·     Genotyping assay for congenital hydrocephalus

 

Market:

In the United States, the health care costs for congenital hydrocephalus are estimated at $100 million per year.

 

Development Status:

In vitro data are available.

 

Publications:

1.     Perry J. Blackshear et al. Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4. Development. 2003 Oct;130(19):4539-4552.  [PubMed abs]

2.     Donghui Zhang et al. Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development. J Neurochem. 2006 Aug;98(3):860-875.  [PubMed abs]

3.     Donghui Zhang et al. Regulatory factor X4 variant 3 (RFX4_v3): a transcription factor involved in brain development and disease. Submitted for publication, Journal of Neuroscience Research.

Early Stage

·     PCT Application No. PCT/US03/12348 filed 18 Apr 2003, which published as WO 03/088919 on 30 Oct 2003 (HHS Reference No. E-163-2002/2-PCT-01)

·     U.S. Patent Application No. 10/511,362 filed 15 Oct 2004, which published as US 2005/0181369 on 18 Aug 2005 (HHS Reference No. E-163-2002/2-US-02)

 

Inventors:

Perry J. Blackshear, Darryl C. Zeldin, Joan P. Graves, and Deborah J. Stumpo (NIEHS)

Licensees Sought:

Available for exclusive or nonexclusive licensing.