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| Status |
Public on Jul 08, 2020 |
| Title |
Multiexon deletion alleles of ATF6 linked to achromatopsia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Achromatopsia (ACHM) is an autosomal recessive disease that results in severe visual loss. Symptoms of ACHM include impaired visual acuity, nystagmus, and photoaversion starting from infancy; furthermore, ACHM is associated with bilateral foveal hypoplasia and absent or severely reduced cone photoreceptor function on electroretinography. Here, we performed genetic sequencing in 3 patients from 2 families with ACHM, identifying and functionally characterizing 2 mutations in the activating transcription factor 6 (ATF6) gene. We identified a homozygous deletion covering exons 8–14 of the ATF6 gene from 2 siblings from the same family. In another patient from a different family, we identified a heterozygous deletion covering exons 2 and 3 of the ATF6 gene found in trans with a previously identified ATF6 c.970C>T (p.Arg324Cys) ACHM disease allele. Recombinant ATF6 proteins bearing these exon deletions showed markedly impaired transcriptional activity by qPCR and RNA-Seq analysis compared with WT-ATF6. Finally, RNAscope revealed that ATF6 and the related ATF6B transcripts were expressed in cones as well as in all retinal layers in normal human retina. Overall, our data identify loss-of-function ATF6 disease alleles that cause human foveal disease.
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| Overall design |
Comparisons of the transcriptomes of transfected HEK293 cells overexpressing WT or mutant ATF6 alleles compared to non-transfected cells.
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| Contributor(s) |
Chiang WJ, Grandjean JM, Lee E, Powers ET, Wiseman RL, Lin JH |
| Citation(s) |
32271167 |
| Submission date |
Jul 07, 2020 |
| Last update date |
Oct 07, 2020 |
| Contact name |
R. Luke Wiseman |
| Organization name |
The Scripps Research Institute
|
| Department |
Molecular Medicine
|
| Lab |
Wiseman
|
| Street address |
10550 North Torrey Pines Road
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA644639 |
| SRA |
SRP270824 |
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