The analyses indicate a very severe phenotype for the patients with the R116W and R173W mutations, and severe for R167W and V215E.
These mice have a homozygous mutation (D257A) in the proofreading domain of mtDNA polymerase γ, significantly reducing its proofreading activity and resulting in the accelerated accumulation of mtDNA mutations and severe respiratory chain deficiency (Trifunovic et al., 2004; Kujoth et al., 2005).
We expect the functional consequences of stop codon polymorphisms (SCPs)—in particular PTCs on the affected gene to be at least as severe as those caused by nonsynonymous mutations and more severe than those caused by synonymous mutations.
Several single-nucleotide polymorphisms and mutations were identified and severe impairment of protein function was observed for three non-synonymous variants.
Thus, other factors may contribute to the penetrance and/or expressivity of de novo ASXL3 mutations in humans, and severe phenotypes could be atypical.
In these patients, in replicating tissues such as blood, there is selection against those cells with high levels of mtDNA mutation and the most severe biochemical defect (Rajasimha et al., 2008), supporting an effect of the RC deficiency on cell proliferation and apoptosis.
Patients with this mutation show a typical and severe clinical course, with early onset, high frequency and short duration of attacks, and high percentages of fever and serositis.
We investigated whether a correlation may exist between a positive qPCRgyrALp assay, the presence of gyrA83 mutations in respiratory samples and severe legionellosis evolution (Table 2).
Follow-up of patients, presenting an early onset of the disease and severe mutations, seems essential to perform accurate genotype phenotype correlations and further characterisation of pathological ABCA4 alleles.
