Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2

Petrovičová, Andrea; Brozman, M; Kurča, Egon; Gobo, Tibor; Dluha, Jana; Kalmarova, Klaudia; Nosáľ, Vladimír; Hikkelova, Martina; Krajčiová, Adriána; Burjanivová, Tatiana; Sivák, Štefan

doi:10.5507/bp.2016.066

Cited by 8 publications

(4 citation statements)

References 25 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found very similar results for Ca V 2.1 selectivity filter mutants, except that trafficking of Ca V 2.1 E I, II, III, IV A was even more severely compromised than for the equivalent Ca V 2.2 mutant, suggesting that trafficking of this channel is very sensitive to interference with the structural integrity of the selectivity filter. It is of great interest that two CACNA1A EA2 missense mutations have been identified that convert the selectivity filter glutamate in domain IV either to the oppositely charged lysine (Denier et al, 2001) or to glycine (Petrovicova et al, 2017). We found that the Ca V 2.1 E IV A mutant (Figure 7D) and the Ca V 2.2 E IV K mutant (Figure 4) exhibited very little surface expression.…”

Section: Discussionmentioning

confidence: 88%

Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 88%

Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In general, missense mutations are associated with FHM1 and trinucleotide (CAG) expansions associated with SCA6. However, a number of reports more recently have identified a significant lack of genotype-phenotype correlation, for example, missense mutations causing EA2 [ 5 – 7 ]. Also reported is the significant variability of clinical phenotype within families who have the same underlying mutation [ 8 ], a complex feature of the CACNA1A gene which is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

A Novel CACNA1A Nonsense Variant [c.4054C>T (p.Arg1352⁎)] Causing Episodic Ataxia Type 2

Lance

Mossman

Poke

2018

Case Reports in Neurological Medicine

View full text Add to dashboard Cite

Episodic ataxia is a heterogenous group of uncommon neurological disorders characterised by recurrent episodes of vertigo, dysarthria, and ataxia for which a variety of different genetic variations have been implicated. Episodic ataxia type two (EA2) is the most common and also has the largest number of identified causative genetic variants. Treatment with acetazolamide is effective in improving symptoms, so accurate diagnosis is essential. However, a large proportion of patients with EA2 have negative genetic testing. We present a patient with a typical history of EA2 who had a novel variant in the CACNA1A gene not previously described. Report of such variations is important in learning more about the disease and improving diagnostic yield for the patient.

show abstract

“…Two such mutations in α 1A are known to occur at the same glutamate in Repeat IV. Mutation of this residue to glycine causes ataxia and cognitive deficits running through three generations of the Slovak family (E1755G in Petrovicova et al, 2017), and as noted above, a reversal of charge via substitution of a lysine for the glutamate causes EA2 (E1761K in Denier et al, 2001). The glutamate to lysine mutation ablates inward Ba 2+ flux via the channel in Xenopus oocytes (Jeng et al, 2006).…”

Section: Familial Hemiplegic Migraine Typementioning

confidence: 90%

Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies

Tyagi

Ribera

Bannister

2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The P/Q-type Ca V 2.1 channel regulates neurotransmitter release at neuromuscular junctions (NMJ) and many central synapses. CACNA1A encodes the pore-containing α 1A subunit of Ca V 2.1 channels. In humans, de novo CACNA1A mutations result in a wide spectrum of neurological, neuromuscular, and movement disorders, such as familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), as well as a more recently discovered class of more severe disorders, which are characterized by ataxia, hypotonia, cerebellar atrophy, and cognitive/developmental delay. Heterologous expression of Ca V 2.1 channels has allowed for an understanding of the consequences of CACNA1A missense mutations on channel function. In contrast, a mechanistic understanding of how specific CACNA1A mutations lead in vivo to the resultant phenotypes is lacking. In this review, we present the zebrafish as a model to both study in vivo mechanisms of CACNA1A mutations that result in synaptic and behavioral defects and to screen for effective drug therapies to combat these and other Ca V 2.1 channelopathies.

show abstract

Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2

Cited by 8 publications

References 25 publications

Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking

Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking

A Novel CACNA1A Nonsense Variant [c.4054C>T (p.Arg1352⁎)] Causing Episodic Ataxia Type 2

Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies

Contact Info

Product

Resources

About