Identification of a novel <i>CACNA1F</i> mutation in a Chinese family with CORDX3

Du, Meng; Li, Yang; Zheng, Panpan; Zhong, Liang; Zhao, Wei; Zhang, Yuxin; Gu, Hanming; Li, Xue; Liu, Zanchao

doi:10.1002/mgg3.2060

Cited by 3 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cav1.4 additionally participates in development of the synapse as disruption of Cav1.4 coincides with a failure in ribbon elongation and loss or mislocalization of numerous associated proteins ( Liu et al, 2013 ; Zabouri and Haverkamp, 2013 ; Maddox et al, 2020 ). In humans, mutations in Cav1.4 subunits result in a spectrum of visual disorders from incomplete stationary night blindness (CSNB2) to progressive cone-rod dystrophy ( Hauke et al, 2013 ; Michalakis et al, 2014 ; De Silva et al, 2021 ; Du et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, many patients do not have night blindness leading to the use of the alternative names cone-rod synaptic disorder or congenital stationary synaptic dysfunction ( Boycott et al, 2000 ; Littink et al, 2009 ; Bijveld et al, 2013 ; Stone et al, 2017 ). Some people with CACNA1F mutations have been diagnosed with cone-rod dystrophy ( Jalkanen et al, 2006 ; Hauke et al, 2013 ; Du et al, 2022 ). The range of retinal dysfunction associated with CACNA1F mutations is consistent with mouse models where both gain-of-function and loss-of-function mutations impair rod and cone synapses ( Mansergh et al, 2005 ; Chang et al, 2006 ; Doering et al, 2008 ; Specht et al, 2009 ; Knoflach et al, 2013 ; Regus-Leidig et al, 2014 ; Dai et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mouse all-cone retina models of Cav1.4 synaptopathy

Laird¹,

Kopel²,

Lankford³

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The voltage-gated calcium channel, Cav1.4 is localized to photoreceptor ribbon synapses and functions both in molecular organization of the synapse and in regulating release of synaptic vesicles. Mutations in Cav1.4 subunits typically present as either incomplete congenital stationary night blindness or a progressive cone-rod dystrophy in humans. We developed a cone-rich mammalian model system to further study how different Cav1.4 mutations affect cones. RPE65 R91W KI; Nrl KO “Conefull” mice were crossed to Cav1.4 α1F or α2δ4 KO mice to generate the “Conefull:α1F KO” and “Conefull:α2δ4 KO” lines. Animals were assessed using a visually guided water maze, electroretinogram (ERG), optical coherence tomography (OCT), and histology. Mice of both sexes and up to six-months of age were used. Conefull: α1F KO mice could not navigate the visually guided water maze, had no b-wave in the ERG, and the developing all-cone outer nuclear layer reorganized into rosettes at the time of eye opening with degeneration progressing to 30% loss by 2-months of age. In comparison, the Conefull: α2δ4 KO mice successfully navigated the visually guided water maze, had a reduced amplitude b-wave ERG, and the development of the all-cone outer nuclear layer appeared normal although progressive degeneration with 10% loss by 2-months of age was observed. In summary, new disease models for studying congenital synaptic diseases due to loss of Cav1.4 function have been created.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mouse all-cone retina models of Cav1.4 synaptopathy

Laird¹,

Kopel²,

Lankford³

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

Identification of a novel CACNA1F mutation in a Chinese family with CORDX3

Du¹,

Li²,

Zheng³

et al. 2022

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background: X-linked cone-rod dystrophy (CORDX) is one form of inherited retinal disorders (IRDs) characterized by progressive dysfunction of photoreceptor. Three types of CORDX were reported and CACNA1F gene defect can cause CORDX3. The aim of this study was to investigate the pathogenic variant in a Chinese family with IRD. Methods:The two affected subjects including the proband and his elder sister underwent ophthalmic examinations. Whole exome sequencing (WES) was performed in the proband at first, then co-segregation analysis was performed in the family by Sanger sequencing. Minigene approach was used to verify the effect of the mutation on the splicing of CACNA1F. X-chromosomal inactivation assay was performed to evaluate the inactivation patterns of the female carriers. Results: The ophthalmic examination results of the proband fit the clinical description of CORDX3, and the female patient presented with only mild symptoms due to mildly skewed X-chromosomal inactivation (ratio 67: 33). Molecular genetic testing identified a novel splice-site mutation c.3847-2A > G in CACNA1F (NM_005183.4) gene in the patients, which inherited from their asymptomatic mother. Minigene approach confirmed that c.3847-2A > G could affect the splicing of CACNA1F. Conclusion: Our study identified a novel splice-site mutation in the CACNA1F gene, which expanded the mutational spectrum of CACNA1F-releated diseases and demonstrated the importance of combining clinical and genetic testing in the diagnosis of IRDs.

show abstract

A novel variant in the SPTB gene underlying hereditary spherocytosis and a literature review of previous variants

Wang,

Liu,

Jia

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

Background Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant’s pathogenicity and reveal a patient’s genetic etiology. Methods The clinical data of a patient with HS who underwent genetic sequencing at the Children’s Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results A novel variant (c.301–2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301–2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-024-01973-w.

show abstract

Identification of a novel CACNA1F mutation in a Chinese family with CORDX3

Cited by 3 publications

References 33 publications

Mouse all-cone retina models of Cav1.4 synaptopathy

Mouse all-cone retina models of Cav1.4 synaptopathy

Identification of a novel CACNA1F mutation in a Chinese family with CORDX3

A novel variant in the SPTB gene underlying hereditary spherocytosis and a literature review of previous variants

Contact Info

Product

Resources

About