This project involves the study of a novel familial neurodegenerative disorder, presenile familial dementia with neuroserpin inclusion bodies (FDNIB). This disorder, which has a characteristic clinical course of progressive dementia and neurologic involvement, was defined in one extended family. Neuroserpin is a strong candidate gene for this disorder and a mutation is present in this large kindred. This project will characterize the clinical phenotype, delineate the natural history of the disorder and explore genotype/phenotype correlation in the index family. Families with immunohistopathologically-neuroserpin positive neuronal inclusion on autopsy/biopsy in an affected member(s) or with familial presenile dementia with neurologic features consistent with the original FDNIB family will be enrolled. Participating family members will undergo periodic clinical assessment for the purpose of: 1) definition and characterization of the phenotype, 2) determination of the natural history of the disorder, 3) genotype/phenotype correlation, and 4) determination of the underlying molecular and biochemical defect.
| El-Jaick, Kenia B; Powers, Shannon E; Bartholin, Laurent et al. (2007) Functional analysis of mutations in TGIF associated with holoprosencephaly. Mol Genet Metab 90:97-111 |
| Bendavid, C; Haddad, B R; Griffin, A et al. (2006) Multicolour FISH and quantitative PCR can detect submicroscopic deletions in holoprosencephaly patients with a normal karyotype. J Med Genet 43:496-500 |
