|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Of note, 2 heterozygous missense variants (c.1438C>T, p.R480 W; c.1309C>G, p.R437G), both lying in the second spectrin repeat of SPTBN2, have been linked to infantile-onset cerebellar ataxia, similar to SCAR14.
|
31617442 |
2020 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Our findings indicate that SPTBN2 mutations may be associated with infantile-onset cerebellar ataxia accompanied with global developmental delay.
|
30898343 |
2019 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Moreover, the novel mutation, p.R414C, adds up to the literature for the infantile-onset form of autosomal recessive ataxia associated with SPTBN2.
|
29196973 |
2018 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
To date, only two other SPTBN2 mutations with recessive pattern of inheritance causing SCAR14 (spinocerebellar ataxia, autosomal recessive 14) that manifest with developmental ataxia and cognitive impairment, or cerebellar ataxia, mental retardation, and pyramidal signs have been reported.
|
28636205 |
2017 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Heterozygous mutations in the gene encoding β-III spectrin (SPTBN2) underlie SCA type-5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type-1 (SPARCA1), an infantile form of ataxia with cognitive impairment.
|
26821241 |
2016 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family.
|
23838597 |
2014 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
This suggests impaired ability to form stable complexes between the adaptor protein ankyrin R and its interacting partners in the Purkinje cell dendritic tree is a key mechanism by which mutant forms of β-III spectrin cause ataxia, initially by Purkinje cell dysfunction and exacerbated by subsequent cell death.
|
24603075 |
2014 |
|
Cerebellar Ataxia
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype.
|
23236289 |
2012 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Additionally, pure cerebellar ataxias, which represent up to 20% of all ataxias, remain poorly studied with only two causative dominant genes being described: CACNA1A (ref.9) and SPTBN2 (ref.10).
|
17159980 |
2007 |
|
Cerebellar Ataxia
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Recently, betaIII spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co-workers of pathogenic mutations in the SPTBN2 gene in three large (and mapped) SCA5 families of American and European origin.
|
16927298 |
2006 |