Biochemical Genetics

, Volume 57, Issue 4, pp 540–554 | Cite as

A Novel CNGA1 Gene Mutation (c.G622A) of Autosomal Recessive Retinitis Pigmentosa Leads to the CNGA1 Protein Reduction on Membrane

  • Qing Gao
  • Yifan Liu
  • Xinlan Lei
  • Qinqin Deng
  • Yongqing Tong
  • Lique Du
  • Yin ShenEmail author
Original Article


CNGA1 encodes a membrane protein on rod photoreceptor related to phototransduction. The present study was to identify a novel mutation of CNGA1 associated with autosomal recessive retinitis pigmentosa by using next generation sequencing of a Chinese family. Next generation sequencing and Sanger sequencing has identified a compound heterozygous mutation in CNGA1 gene, c0.472 del C (reported) and c0.829G>A (novel mutation, same as c0.622G>A according to NM_000087.3) of the proband. SIFT and Polyphen-2 predicted the CNGA1 G622A site to be possibly deleterious. Evolutionary conservation analysis of amino acid residues showed this aspartic acid is highly conserved between species, and protein structure prediction by I-TASSER server indicated that the D208N mutation induced a large disappear of interactions between S2 and S4. Flag-tagged CNGA1 and mutant G622A cDNA were generated and inserted into pCIG-eGFP vectors. Transfection of human embryonic kidney 293T cells was performed with lipofectamine. Interestingly, western blot and immunofluorescence results indicated that the expression of mutant CNGA1 (D208N) decreased significantly, especially on the membrane of transfected HEK293T cells. The novel variant c0.622G>A (p. D208N) in this study enriched the CNGA1 mutation spectrum. Besides, this mutant was predicted “possibly damaging” due to bioinformatics analysis and validated by laboratorial experiments. Our study suggests that this mutation lead to the CNGA1 protein reduction from the cell membrane.


Retinitis pigmentosa Cyclic nucleotide gated channel alpha 1 Next generation sequencing 



We thank Ting Xie, the professor of the Stowers Institute for Medical Research for proof reading. We thank professor Xing Jian for the technique support in molecular modeling. Work was funded by The National Nature Science Foundation of China (Grant No. 81470628), International Science and Technology Cooperation Program of China (2017YFE0103400) and Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science (2017B030314025).

Compliance with Ethical Standards

Conflict of interest:

The authors declare that they have no conflict of interest.

Supplementary material

10528_2019_9907_MOESM1_ESM.docx (1.7 mb)
Supplementary file1 (DOCX 1780 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Qing Gao
    • 1
  • Yifan Liu
    • 1
  • Xinlan Lei
    • 1
  • Qinqin Deng
    • 1
  • Yongqing Tong
    • 2
  • Lique Du
    • 3
  • Yin Shen
    • 1
    Email author
  1. 1.Eye CenterRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Clinical LaboratoryRenmin Hospital of Wuhan UniversityWuhanChina
  3. 3.BGI-WuhanWuhanChina

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