These murine models recapitulate the salient features of human NEB mutation, including severe muscle weakness, impaired force generation and histopathological changes including reduced thin filament length and the presence of nemaline rods and bodies.
This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.
In contrast to the heterozygous LMNA p.R435C mutation, which expresses a rather mild clinical picture if any, the patient harboring the homozygous mutation presents clinically with a severe progeroid syndrome including severe skin abnormalities as pathognomonic symptoms.
Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation.
Costello mutations include the severe HRasG12V mutation, which we modeled.
One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown.
SCN1A mutations related to Dravet syndrome include severe disruptions of channel integrity (e.g. frameshift mutations, deletions), and, less commonly, missense mutations leading to either channel impairment or gain of function.
A previous study revealed five homozygous WDR62 mutations, including deletions and premature terminations, in patients of Turkish origin suffering from severe brain malformations and microcephaly [ 30].
In theory, silent mutations including mutations in noncoding regions and synonymous mutations in coding regions have less severe phenotypic effects than non-synonymous mutations, changing the amino-acid composition.
ROR2-deficient mice exhibited severe skeletal defects which are analogous to those of human RS mutations including dwarfism as well as heart and lung malformation [6], [7].
