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Molecular Diagnostics and Protein Unit
The Unit of Molecular Diagnostics and Protein evolved from the specific protein laboratory which was under the Biochemistry Division since 1980. The Protein Laboratory was developed to be the reference centre for Multiple Myeloma Protein Profiling in Malaysia. With the reorganization of IMR in year 2000, the Protein Laboratory was upgraded to “Molecular Diagnostics and Protein Unit” under the Specialized Diagnostics Centre and given the responsibility to develop molecular diagnostics in genetic diseases particularly IEM, besides maintaining as the reference centre for Multiple Myeloma Protein Profiling. The unit has developed further in the two main focus areas through research and development of new specialized diagnostics testing. Molecular genetics diagnostics started with mutational analysis of OTC gene for urea cycle defect. The two focus areas now are as a Reference Laboratory in Multiple Myeloma and Paraproteinemia, and a Centre of Excellence for Molecular Diagnostics for Genetic Diseases and Mitochondrial Disorders including IEM.
It was in 2003 with a “Dasar Baru in IEM” and with the acquisition of sequencing facilities that molecular genetics has developed further to encompass mitochondrial disorders such as Leigh syndrome, LHON and other mutation points for MELAS, MERFF and NARP. Subsequently IMR has expanded the mutational analysis of the whole mitochodrial genome of 16.5 kilobases which encodes 13 essential polypeptides of respiratory chain and the 24 tRNAs required for intramitochondrial protein synthesis. These include Complex l genes, Complex lll genes, Complex lV genes and Complex V genes. Mutations in this genome are recognised as an important cause of disease and over 200 different pathogenic defects (point mutation or large scale rearrangements) have been identified. Pathogenic mitochondrial DNAs (mtDNA) are frequently heteroplasmic, with mutated and wild type coexisting in the same cell. We have also initiated studies in nucleic genes that are now known to be linked to mitochondrial disorders such as SURF l and NDUFS genes.
Other genes that have been analysed for mutations include ETHE 1 (Ethylmalonic acidemia), MSUD, CPT11; CGG repeats in FRAXA and FRAXE genes (Fragile X syndrome). A study has also looked into the methylation status of these genes that are found to be contributing factors to the pathogenicity of the disorders. We have also recently initiated a study on the three genes (GLDC, AMT AND GCSH) responsible for NKH (Non-Ketotic Hyperglycinemia).
Besides molecular genetics diagnostics, the Unit has also offered Transferrin phenotyping tests for CDG syndrome and plans to extend further into proteomic characterisation of the different pathogenic isotypes that we have identified in Malaysia.
The year 2007 saw a number of new diagnostic services being developed and offered as new specialized tests such as Free Light Chain Ratios for Light Chain Multiple Myeloma Disease and CSF oligoclonal band phenotyping. These also include mutational analyses of SURF 1 gene (nucleic gene) for Leigh Syndrome, AMT gene for Non-Ketotic Hyperglicinemia and Mutational analysis of mitochondrial coding region for ND2, COX l dan COX ll including 7 tRNAs.
The unit is funded for three ongoing and one new research projects.