Developmental malformations of the cerebellum are common birth defects that often cause mental retardation or developmental delay, in addition to motor and visual handicaps. The most frequent cerebellar malformation is Dandy-Walker malformation (DWM), which is defined by hypoplasia of the cerebellar vermis, dilatation of the fourth ventricle, and often hydrocephalus. Although common, the specific causes of DWM remain undefined. While it is certain that environmental teratogens can cause DWM during embryogenesis, there is clear evidence that as yet undefined genetic factors are also responsible. The investigators have identified several DWM patients with chromosomal abnormalities. In particular, a subset of these patients has overlapping chromosomal deletions defining a small critical region that is hypothesized to identify a DWM locus. The experiments outlined in this application are focused on mutational and functional analysis of two excellent candidate genes, likely causative of DWM. To model DWM, the investigators will construct targeted mouse mutants for these two DWM candidate genes and assess the role of these genes during cerebellar development, based on the hypothesis that similar mechanisms underlie mouse and human CNS development. The identification of a DWM gene will represent a significant advance in the understanding of this common and often devastating brain malformation. It will also provide valuable diagnostic and prognostic information that can greatly influence treatment and genetic counseling. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD044085-01A1
Application #
6725660
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Oster-Granite, Mary Lou
Project Start
2003-12-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2004-11-30
Support Year
1
Fiscal Year
2004
Total Cost
$76,250
Indirect Cost
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637