Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The Timothy syndrome mutation is a rare de novo gain-of-function variant in CACNA1C that causes autism with high penetrance, providing a powerful avenue into investigating the role of CACNA1C variants in neurodevelopmental disorders.
|
31805042 |
2019 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II-III loop.
|
31408100 |
2019 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
To our knowledge, this patient is the first to exhibit syndactyly and to carry a CACNA1C mutation but to not have QT prolongation, which has long been considered an obligatory feature of Timothy syndrome.
|
29736926 |
2018 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
A multicentre study of patients with Timothy syndrome.
|
28371864 |
2018 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Emerging therapeutic targets in the short QT syndrome.
|
29697308 |
2018 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome.
|
28753255 |
2018 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing.
|
27868338 |
2017 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
TRPM4 enlarges the subgroup of LQT genes (KCNJ2 in Andersen syndrome and CACNA1C in Timothy syndrome) known to increase the QT interval through a more complex pleiotropic effect than merely action potential alteration.
|
28315637 |
2017 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Timothy syndrome (TS) is a congenital long QT syndrome that is associated with syndactyly and mutations in CACNA1C, encoding an L-type voltage-dependent calcium channel, Cav1.2.
|
27593853 |
2016 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Comprehensive review and topological mapping of all described CACNA1C mutations revealed TS-specific hotspots localizing to the cytoplasmic aspect of 6th transmembrane segment of respective domains.
|
27390944 |
2016 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Through expanded whole exome sequencing, we identified a novel genetic substrate for TS, p.Ile1166Thr-CACNA1C.
|
25260352 |
2015 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Through whole exome sequencing and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and congenital heart defects annotated as cardiac-only Timothy syndrome.
|
26253506 |
2015 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Whole exome sequencing revealed a novel CACNA1C mutation, p.Ile1166Thr, in a young male with diagnosed TS.
|
25260352 |
2015 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Through whole exome sequencing and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and congenital heart defects annotated as cardiac-only Timothy syndrome.
|
26253506 |
2015 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype.
|
26204268 |
2015 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Classical Timothy syndrome type 1 (TS1) results from a recurrent de novo CACNA1C mutation, G406R in exon 8 A.
|
25691416 |
2015 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We conclude that genotype-negative LQTS patients should be investigated for mutations in CACNA1C, as a gain-of-function in Cav1.2 is likely to cause LQTS and only specific and rare mutations, i.e. in exon 8, cause the multi-systemic TS.
|
25633834 |
2015 |
Timothy syndrome
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
This study aimed to elucidate the frequency of CACNA1C mutations in patients with long QT syndrome (LQTS), except those with Timothy syndrome and investigate phenotypic variants.
|
24728418 |
2014 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD.
|
24752249 |
2014 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This study aimed to elucidate the frequency of CACNA1C mutations in patients with long QT syndrome (LQTS), except those with Timothy syndrome and investigate phenotypic variants.
|
24728418 |
2014 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells.
|
23979604 |
2014 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS), and Timothy syndrome (TS).
|
25184293 |
2014 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Although full TS1 is caused by a single missense mutation in the CACNA1C-encoded cardiac calcium channel, mosaic TS1 parents can display isolated syndactyly without additional phenotypic manifestations.
|
23690510 |
2013 |
Timothy syndrome
|
1.000 |
GermlineCausalMutation
|
disease |
ORPHANET |
Genotype- and phenotype-guided management of congenital long QT syndrome.
|
24093767 |
2013 |
Timothy syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The identification of a gain-of-function mutation in CACNA1C as the cause of Timothy Syndrome (TS), a rare disorder characterized by cardiac arrhythmias and syndactyly, highlighted unexpected roles for the L-type voltage-gated Ca2+ channel CaV1.2 in nonexcitable cells.
|
23549079 |
2013 |