Multiexon deletion alleles of ATF6 linked to achromatopsia

• Eun-Jin, Lee

• Wei-Chieh Jerry, Chiang

• Heike, Kroeger

• Chloe Xiaoke, Bi

• Daniel L., Chao

• Dorota, Skowronska-Krawczyk

• Rebecca R., Mastey

• Stephen H., Tsang

• Leon, Chea

• Kyle, Kim

• Scott R., Lambert

• Julia M.D., Grandjean

• Britta, Baumann

• Isabelle, Audo

• Susanne, Kohl

• Anthony T., Moore

• R. Luke, Wiseman

• Joseph, Carroll

• Jonathan H., Lin

抄録

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.

source:https://insight.jci.org/articles/view/136041

収録刊行物

• JCI Insight

  JCI Insight 5 (7), e136041-, 2020-04-09

  American Society for Clinical Investigation

詳細情報

• CRID: 1051975278388795904
• NII論文ID: 120006900837
• ISSN: 23793708
• Web Site: http://id.nii.ac.jp/1394/00001606/
• 本文言語コード: en
• 資料種別: journal article
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