Mutations in Diaphyseal Medullary Stenosis- Malignant Fibrous Histiocytoma Related Gene MTAP Affects Expression of Splice Variants SV2 and SV5

Diaphyseal Medullary Stenosis- Malignant Fibrous Histiocytoma (DMS-MFH) is a rare autosomal dominant bone syndrome. Thirty-five percent of patients diagnosed with DMS-MFH are at risk of developing a bone sarcoma, malignant fibrous histiocytoma (MFH). Symptoms of this bone disease include bone infarctions, bone pain, leg weakness, and the development of early-onset cataracts. Recently, studies in our laboratory have shown that either of two inherited mutations, IVS8 (-2) A>G or Ex9 (+72) A>G in the MTAP gene locus, results in the development of DMS-MFH. These mutations specifically target the methylthioadenosine phosphorylase (MTAP) gene, located on chromosome 9p21.3. Our laboratory has now shown that the MTAP gene encodes six alternative splicing isoforms