Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W

  title={Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W},
  author={Jean B. Peloquin and Renata Rehak and Clinton J. Doering and John E. McRory},
Congenital stationary night blindness in mice - a tale of two Cacna1f mutants.
Cacna1f ( G305X) is a true knockout model for human CSNB2, with prominent defects in cone and rod function, because alternative splicing in an ETn element leads to some full-length Ca(v)1.4 protein, and some cones surviving to drive photopic visual responses.
Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2
The hypothesis that a hyperpolarizing shift in the voltage-dependence of channel activation—as seen in the IT gain-of-function mutant2—may reduce the dynamic range of photoreceptor activity is supported.
Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness.
The results expand the mutation spectrum of NYX, CACNA1F, NYX and GRM6 and suggest that NYX mutations are a common cause of CSNB.
A Review of Genetic and Physiological Disease Mechanisms Associated With Cav1 Channels: Implications for Incomplete Congenital Stationary Night Blindness Treatment
It is highlighted that therapeutic treatments for each of the Cav1 channels will have to consider channel-specific mechanisms, especially for the treatment of X-linked iCSNB.
Functional impact of a congenital stationary night blindness type 2 mutation depends on subunit composition of Cav1.4 Ca2+ channels
It is concluded that the IT mutation stabilizes channel opening and alters ion selectivity of Cav1.4 in a manner that is strengthened by exclusion of exon 47 and inclusion of β2X13 and α2δ-4.
An Ashkenazi Jewish founder mutation in CACNA1F causes retinal phenotype in both hemizygous males and heterozygous female carriers
The data suggests that p.(F742C) in CACNA1F is an X-linked founder mutation in Ashkenazi Jews originating in Eastern Europe, which causes a mild-to-moderate icCSNB phenotype, expressed in most female carriers.
Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease
To identify the disease genes behind the cone-rod dystrophy and AIED phenotypes, and to determine the functional consequences of the mutations identifi ed, the aims of this study were to map the disease gene in a large Finnish family with X-linked cone- Rod Dystrophy, and discover a novel CACNA1F gene mutation in AIED patients.
Voltage-Gated Ca2+-Channel α1-Subunit de novo Missense Mutations: Gain or Loss of Function – Implications for Potential Therapies
  • J. Striessnig
  • Biology, Medicine
    Frontiers in Synaptic Neuroscience
  • 2021
This review summarizes the current knowledge of human disease-relevant genetic variants within the family of voltage gated Ca2+ channels and focuses on the rapidly increasing number of de novo missense mutations identified in the pore-forming α1-subunits with next generation sequencing studies of well-defined patient cohorts.
Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels
The role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies) is summarized and exciting disease-related molecular detail that led to important novel insight not only into disease pathophysiology but also to mechanisms of channel function is provided.


Congenital Stationary Night Blindness Type 2 Mutations S229P, G369D, L1068P, and W1440X Alter Channel Gating or Functional Expression of Cav1.4 L-type Ca2+ Channels
The authors' data provide unequivocal evidence that CSNB2 missense mutations can induce severe changes in Cav1.4 function, which may decrease (L1068P and S229P) or even increase (G369D) channel activity and the lower activation range of G369D can explain the reduced dynamic range of photoreceptor signaling.
Effects of congenital stationary night blindness type 2 mutations R508Q and L1364H on Cav1.4 L‐type Ca2+ channel function and expression
The data provide evidence that, in contrast to previously characterized CSNB2 missense mutations, the clinical phenotype of R508Q and L1364H is unlikely to be explained by changes in channel gating, and instead, these mutations affect the protein expression of Cav1.4 Ca2+ channels.
A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants
In characterizing transcripts of CACNA1F, several splice variants are identified and a prototypical sequence is defined based on the location of mutations in spliced variants and comparison with the mouse orthologue, Cacna1f.
Mutations in the CACNA1F and NYX genes in British CSNBX families
The report of patient population mutation screening for both CSNBX genes, and the exclusion of RP2 and RGPR, indicates that mutations in CACNA1F and NYX are likely to account for all CS NBX.
Novel CACNA1F mutations in Japanese patients with incomplete congenital stationary night blindness.
Mutations in the retina-specific calcium channel alpha1-subunit gene (CACNA1F) in Japanese patients with incomplete CSNB are reported, leading to the conclusion that in most Japanese patients, incomplete CS NB is caused by a CACNA 1F mutation.
Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness
It is established that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.
An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness
The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific
Novel mutations in CACNA1F and NYX in Dutch families with X-linked congenital stationary night blindness.
In a pool of eight diagnosed X-linked congenital stationary night blindness patients, five showed a sequence variation in the CACNA1F and two in the NYX gene and in only one of the eight patients no sequence alteration could be detected.