It is also possible to find subjects with gain-of-function mutations
in seipinopathies, a dominant condition that needs at least one mutated allele to manifest the phenotypical condition (Figures 7(d) and 7(e)).
Kiykim et al., "Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations
in STAT1," Journal of Clinical Immunology, vol.
The clinical observations and genetic tests further revealed that the gain-of-function mutations
of EAG1 channels are closely associated with two rare neuronal developmental diseases Zimmermann-Laband and Temple-Baraitser syndromes (ZLS and TBS) [21-24].
These facts suggested that ASXL1 mutations are dominant-negative or gain-of-function mutations
. (85) Consistent with this, we have shown that bone marrow cells transduced with the C-terminal truncated ASXL1 mutant (ASXL1-MT) induced MDS-like symptoms in the transplanted mice (Fig.
It is well established that dysregulation of the alternative complement pathway is involved in 60-70% of all cases with loss-of-function mutations in complement regulators such as factor H, factor I, and membrane cofactor protein (MCP/CD46), or gain-of-function mutations
in C3 or factor B .
Jin et al., "Identification of a KCNE2 gain-of-function mutation
in patients with familial atrial fibrillation," American Journal of Human Genetics, vol.
* The defect in type 2B VWD involves a gain-of-function mutation
in VWF; in PT-VWD, there is a gain-of-function mutation
in the GP1b platelet receptor.
In the report cited above, we described the discovery of a second prothrombotic gain-of-function mutation
[the G20210A substitution in the F2 gene, coagulation factor II (thrombin)].
Almost 75% of all GISTs present gain-of-function mutations
in the KIT gene in exons 11, 9, 13, and 17, which activate downstream pathways (RAS/RAF/MAPK, JAK/STAT3, and PI3K/AKT/mTOR), increasing proliferation or evading apoptosis.
XEN901 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed by Xenon for the treatment of epilepsy including treatment resistant adult and pediatric focal seizures, as well as rare, pediatric forms of epilepsy, such as EIEE13, an early infantile epileptic encephalopathy due to gain-of-function mutations
in the SCN8A gene that encodes the Nav1.6 sodium channel.
The fact that all three independent mosaic trisomy 9 syndrome cases were accompanied by HPE supports the notion that HPE may be a symptom of this aneuploidy as well as the suggestion by other researchers that gain-of-function mutations
of the PTCH1 gene may also cause HPE.
The molecular pathogenesis of these tumors includes gain-of-function mutations
in C-kit and PDGFRA, which are both tyrosine kinase receptors.