While the hSyn II mutants described here displayed a predominant loss-of-function character in primary SYN2 KO neurons, their pathogenic role in patients in whom only one allele is mutated could result from either a haploinsufficiency with impaired Syn II expression or a dominant-negative effect towards the endogenous Syn II.
The cone-rod dystrophies (crd) are characterized by a predominant loss of cone function, with relative preservation of rod function [ 13, 14].
Nevertheless, the presence of both hypocalciuria and hypomagnesaemia in the SPAKL502A/L502A mice is in keeping with a predominant loss of NCC function, because the loss of NKCC2 function in the mouse is associated with the opposite phenotype of hypermagnesaemia and hypercalciuria (45).
Sural nerve biopsy from one patient, 2 years after diagnosis showed degeneration of both axon and myelin and a predominant loss of large myelinated fibers.
In the hereditary retinal diseases group, the predominant loss of vision was peripheral and binocular, however, in the acquired retinal diseases group; it was mostly central and monocular.
MECP2 loss-of-function is the predominant cause of Rett syndrome, a postnatal neurological disorder that typically manifests around 18 months of age with developmental regression (Amir et al., 1999; Ravn et al., 2005; Pan et al., 2006).
Knowing that the predominant reason Arabidopsis CNSs go undetectable is deletion, leading to loss-of-function, is crucial for the intelligent application of a new strategy for enhancer-like site analysis: fractionation mutagenesis.
The first two scenarios are shown in Figure 2: a clustered missense mutation landscape with no truncating mutations, implying a typical gain-of-function OG like KRAS; and diffuse and predominant truncating mutations with no missense pattern like APC, underlying a loss-of-function TSG.
Most of the mutations identified were loss-of-function and carriers most often constipation-predominant.
Through a combination of overexpression and loss-of-function approaches, we have identified SENP1 as the predominant SENP acting on Elk-1, and hence placing SENP1 as a key player in determining the transcriptional outcomes to mitogenic signalling.
W.Y. and J.L.R carried out the loss-of-function screen.
