Among these mutations, the nonsense mutation is a severe type that converts a coding codon into a stop codon, leading to the premature termination of translation and the expression of proteins truncated at the carboxyl terminus.
Imaging experiments involving comparisons to strains containing the daf-7 ok3125) daf-7 ok3125ld not be treated as above, as this mutation coulds a severe egg-layinotdefect.
Although strong immunoreactivity with an otoferlin-specific antibody was detected in cochlear hair cells of wildtype mice, no expression was detected in mutant mice, indicating that the missense mutation has a severe effect on the stability of the protein and potentially its localization.
tmem33sh443 mutants display substantially reduced expression of tmem33 mRNA (Supplementary Fig. 7c e) likely via nonsense-mediated decay, indicating this mutation represents a severe loss-of-function or null allele.
This mutation causes a severe translation defect during mitochondrial protein synthesis, which has been attributed to a decrease in the steady-state abundance of the mitochondrial tRNALys, reduced aminoacylation of tRNALys, and lack of a post-transcriptional 5-taurinomethyl 2-thiouridine RNA modification of the anticodon wobble base4,5,6,7.
Mice homozygous for the mk mutation have a severe hypochromic, microcytic anemia that is characterized by a decreased mean-corpuscular hemoglobin concentration and balanced alpha- and beta-globin-chain synthesis.
Nonetheless, the C232S mutation causes a severe LGMD in homozygous patients (Ref. 53).
The most prominent phenotype resulting from vWF mutation is a severe bleeding tendency.
In contrast, patient p1.1 with a mild mutation showed a severe phenotype, featuring only light perception, extensive chorioretinal atrophy and extinguished ERG.
This was also shown in a mouse model, however in this model the mutation had a severe dominant negative effect (Pereira et al., 1997).
