P2-184: Identification of a novel chromosomal locus in a Belgian FTLD-MND family

Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative brain disorder with a prevalence similar to that of Alzheimer's disease in the population below age 65 years. In some patients FTLD symptoms are accompanied by signs of motor neuron disease (MND). A positive family history is observed in up to 50% of FTLD patients indicating a significant contribution of genetics to the etiology of FTLD. A high degree of genetic heterogeneity has been observed with different mutations in the genes encoding the microtubule-associated protein (MAPT), progranulin (PGRN), charged multivesicular body protein 2B (CHMP2B) and valosin containing protein (VCP). Further, two loci on chromosome 9 at 9q21-q22 and 9p13–21 were implicated in FTLD with MND (FTLD-MND). In Belgian familial FTLD patients 65% remained unexplained by mutations in known FTLD genes. Of one patient diagnosed with FTLD-MND, we collected DNA of relatives and performed a genome-wide scan. We identified and finemapped a novel chromosomal locus that was not previously linked to FTLD and/or MND. Haplotype analysis identified a risk haplotype of 23 cM that co-segregated with disease. Further reduction of the candidate region and mutation analyses of positional and functional candidate genes are ongoing. Identification of the mutation in the underlying disease gene will significantly contribute to the understanding of neurodegenerative disease mechanisms in FTLD.