Dmk Synthesis
The nonmutated form of DMPK functions in the production of protein kinase serine; this enzyme plays a role in intracellular communication and in the regulation of myosin phosphate. When DMPK is mutated, the proteins CUG-BP1, MBNL1 and INSR are displaced causing the splicing of troponin pre-mRNA which causes malfunctions in the cardiac conduction system, dominance of a chloride channel that causes myotonia, dominance of an insulin receptor that affects the sufficiency of insulin, and dominance of a tau protein that alters cognitive function (Cho and Tapscott, 2006). In a study by Klesert, Otten, Bird, and Tapscott (1997), a northern blot analysis was done to determine the amounts of DMPK and DMAHP (DM-associated homeo domain protein) present
in skeletal muscle of myotonic dystrophy patients. In the study, when RNA was converted to skeletal muscle, the DMAHP levels decreased while the amount of mutated DMPK increased. DMAHP is a flanking and homeodomain encoding gene (Thornton, Wymer, Simmons, McClain, and Moxley, 1997). From the study mentioned above, it was determined that DMAHP is reduced only in the affected tissues (muscle and myocardium) of myotonic dystrophy patients. Since the mutation in the genes is caused by a repeat expansion of CTG, a study was conducted in 1997 by Thornton, Wymer, Simmons, McClain, and Moxly to determine if the reduction of DMAHP was a direct result of the CTG repeat. This hypothesis was proven to be true by the location of a polymorphic coding sequence in exon 3 of DMAHP. The DMPK gene has been located on chromosome 19 on band 19q13.3. When this gene is mutated and produces the CTG repeat, the affected allele becomes larger than the alleles next to it. While the exact marker on the chromosome that is mutated is unknown, a study showed that DNA markers D19S63 and D19S95 may be the cause (Brook, McCurrach, Harley, Buckler, and Church, 1992). When this mutation is transcribed into mRNA, the CTG repeat is located 500 base pairs from the polyA tract. Myotonic dystrophy type 2 is caused by a mutation in the CNBP gene; this mutation is an expansion of a CCTG repeat. Although the two mutations of the genes in type 1 and type 2 are similar, the two genes are not directly related to each other (Table 1) (Cho and Tapscott, 2006). The CNBP gene been located on chromosome 19 on band 3q21. The CNBP gene produces zinc finger protein 9. ZNF9 is believed to function as an RNA binding protein and it is commonly seen in myofibrils. ZNF9 is not altered in type 2 patients so it is unclear how this gene product produces the phenotypes seen in type 2 patients (Massa et al., 2010). Neither mutation affects the coding portion of these proteins nor is it known how these mutations affect muscle and other organs.
in skeletal muscle of myotonic dystrophy patients. In the study, when RNA was converted to skeletal muscle, the DMAHP levels decreased while the amount of mutated DMPK increased. DMAHP is a flanking and homeodomain encoding gene (Thornton, Wymer, Simmons, McClain, and Moxley, 1997). From the study mentioned above, it was determined that DMAHP is reduced only in the affected tissues (muscle and myocardium) of myotonic dystrophy patients. Since the mutation in the genes is caused by a repeat expansion of CTG, a study was conducted in 1997 by Thornton, Wymer, Simmons, McClain, and Moxly to determine if the reduction of DMAHP was a direct result of the CTG repeat. This hypothesis was proven to be true by the location of a polymorphic coding sequence in exon 3 of DMAHP. The DMPK gene has been located on chromosome 19 on band 19q13.3. When this gene is mutated and produces the CTG repeat, the affected allele becomes larger than the alleles next to it. While the exact marker on the chromosome that is mutated is unknown, a study showed that DNA markers D19S63 and D19S95 may be the cause (Brook, McCurrach, Harley, Buckler, and Church, 1992). When this mutation is transcribed into mRNA, the CTG repeat is located 500 base pairs from the polyA tract. Myotonic dystrophy type 2 is caused by a mutation in the CNBP gene; this mutation is an expansion of a CCTG repeat. Although the two mutations of the genes in type 1 and type 2 are similar, the two genes are not directly related to each other (Table 1) (Cho and Tapscott, 2006). The CNBP gene been located on chromosome 19 on band 3q21. The CNBP gene produces zinc finger protein 9. ZNF9 is believed to function as an RNA binding protein and it is commonly seen in myofibrils. ZNF9 is not altered in type 2 patients so it is unclear how this gene product produces the phenotypes seen in type 2 patients (Massa et al., 2010). Neither mutation affects the coding portion of these proteins nor is it known how these mutations affect muscle and other organs.