Hereditary inclusion body myopathies (h-IBM) are a genetically diverse group of diseases characterized by distal/proximal limb-girdle muscle weakness and the presence of inclusion bodies in muscle. The various forms of h-IBM are devastating muscular disorders lacking a defined pathophyological basis and any effective therapies. We recently identified a new member of this group of disorders [1, 2], in which the inclusion body myopathy is associated with Pagets disease of the bone (PDB) and/or frontotemporal dementia (FTD). This new disorder previously diagnosed as a variety of disorders such as limb girdle muscular dystrophy and amyotropic lateral sclerosis has been categorized as IBMPFD (MIM 605382). The inclusion body myopathy is progressive with onset typically in the 30s-40s and associated with early demise. We have identified a locus on chromosome 9p21.1-p12, plan to identify the gene and simultaneously study the expression profile for autosomal dominant hereditary inclusion body myopathy, and Pagets disease of bone.
The aims of the proposed research project are: (1) To establish a registry of individuals with familial myopathy associated with Paget disease of the bone (IBMPFD) (2) To refine the map placement of the IBMPFD gene by analyzing additional genetic markers within the IBMPFD region in existing and new families for the purpose of more precisely mapping crossovers needed to narrow the diseasecontaining interval. (3) To identify a causal gene for familial myopathy associated with Paget disease of the bone mapping to 9p21.1-p12 (4) Clinical and molecular characterization of a large family from Canada (appendix 10) diagnosed with myopathy and polyostotic fibrous dysplasia and fractures. Elucidation of the genetic defect will help us understand the pathogenesis of this multifaceted disorder and hopefully result in specific therapy. ? ? ?
|Mehta, S G; Khare, M; Ramani, R et al. (2013) Genotype-phenotype studies of VCP-associated inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia. Clin Genet 83:422-31|