Minor patients with two mutations in POLG , DGUOK , TK2 , and SUCLA2 genes showed a wide phenotypic spectrum, including Alpers' syndrome, early-onset hepatocerebral disease, myopathy, and ophthalmoparesis.
28], Among these genes, TK2 , DGUOK , and SUCLA2 genes encode proteins that maintain the mitochondrial dNTP pool, and POLG gene is essential for mtDNA replication.
Of nine patients with a TK2
deficiency, one had been on a ventilator for 24 hours a day, but was now completely off of it, the doctor said.
Mutations in TK2 and SUCLA2 are responsible for the myopathic form of MDDS (4, 9).
2 deleterious mutations): 122 blood, 21 muscle, 15 liver, and 7 skin fibroblast samples from patients with 2 proven mutations in 1 of 8 nuclear genes (POLG, DGUOK, TK2, TYMP, MPV17, SUCLA2, SUCLG1, and RRM2B) known to cause mtDNA depletion.
Ninety-seven samples from symptomatic individuals suspected of having a mitochondrial disorder but with sequence analyses revealing only 1 mutation or an unclassified novel variant were also evaluated for mtDNA depletion (POLG, 59 blood and 6 muscle samples; DGUOK, 16 blood samples; TK2, 1 muscle and 5 blood samples; MPV17, 6 blood samples; TYMP, 4 blood samples) (see Table S4A in the Data Supplement that accompanies the online version of this article at http://www.
The mean mtDNA content in blood samples was reduced to 78% of the control value in samples from individuals with POLG mutations, 52% in those with DGUOK or MPV17 mutations, 79% in those with TK2 mutations, 70% in those with TYMP mutations, and 39% in those with RRM2B mutations (see Table 2A in the online Data Supplement).
The substrate specificity of TK2 is different from that of TK1, e.
125]I, is relatively complex, and partly measures the activity of TK2.
To check that no TK2 enzyme was present in the crude extract, we performed rod electrophoresis, followed by REA detection with the prolifigen[R] TK REA assay (DiaSorin AB), which detects both TK1 and TK2 (32).
These buildings addresses the construction of two pumping stations and sewage systems TK1 and TK2
pressure (displacement) sewerage system.