There was either no defect or only a mild defect of SHM.
Electrophysiological tests showed evidence of synaptic activity in differentiated neurons carrying non-pathogenic mtDNA mutations or in those that caused a mild defect of respiratory activity.
In the present study, we have performed an analysis of the mitochondrial metabolism of neurons containing mtDNA mutations that generate either a mild defect of complex IV or a severe defect of complex I (Kirby et al., 2009).
The phenomenon of mild defect of DSB repair in the absence of H2AX could be explained by the fact that H2AX is not absolutely needed for the concentration of recognition factors MRN and ATM at the damaged sites (Yuan and Chen 2010).
Arg770Glu and Val863Ala, corresponding to human p.Gln968Glu and p.Val1106Ala POLG variants, respectively, are located in the polymerase domain and show a rather mild defect of mtDNA stability (measured by a moderate increase in petite frequency).
A possible explanation for the relative rarity of this CMS is that carriers of two MUSK mutations that result in only mild defect of MuSK protein function may not express clinical symptoms, whereas the presence of a mutation that results in severe deficiency of MuSK function in each of the alleles is probably not compatible with life.
In embryos mutant for either pkg21D allele, somatic muscles were patterned normally with mild defects in extension of the ventral oblique (VO) muscles (Fig. 3B; data not shown).
Mild defects included asymmetry of the head (supplementary material Fig. S1B,E,F,I,J and Fig. S2B,E,H,I) and eye defects including unilateral or bilateral microphthalmia and anophthalmia (supplementary material Fig. S1B,E,F,I,J and Fig. S2B,E,H,I).
Mild defects include irregularly spacing of the ventral nerve cord, some disorganization of the axon scaffold, abnormally thin or thick, and wavy longitudinal connectives.
However, loss of any one of the receptors and/or their ligands results in relatively mild defects compared with loss of the alternative pathway, most likely because the three receptors are partially redundant.
