Zeitz, C;
Méjécase, C;
Michiels, C;
Condroyer, C;
Wohlschlegel, J;
Foussard, M;
Antonio, A;
... Audo, I; + view all
(2021)
Mutated CCDC51 coding for a mitochondrial protein, MITOK is a candidate gene defect for autosomal recessive rod-cone dystrophy.
International Journal of Molecular Sciences
, 22
(15)
, Article 7875. 10.3390/ijms22157875.
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Abstract
The purpose of this work was to identify the gene defect underlying a relatively mild rod-cone dystrophy (RCD), lacking disease-causing variants in known genes implicated in inherited retinal disorders (IRD), and provide transcriptomic and immunolocalization data to highlight the best candidate. The DNA of the female patient originating from a consanguineous family revealed no large duplication or deletion, but several large homozygous regions. In one of these, a homozygous frameshift variant, c.244_246delins17 p.(Trp82Valfs*4); predicted to lead to a nonfunctional protein, was identified in CCDC51. CCDC51 encodes the mitochondrial coiled-coil domain containing 51 protein, also called MITOK. MITOK ablation causes mitochondrial dysfunction. Here we show for the first time that CCDC51/MITOK localizes in the retina and more specifically in the inner segments of the photoreceptors, well known to contain mitochondria. Mitochondrial proteins have previously been implicated in IRD, although usually in association with syndromic disease, unlike our present case. Together, our findings add another ultra-rare mutation implicated in non-syndromic IRD, whose pathogenic mechanism in the retina needs to be further elucidated.
| Type: | Article |
|---|---|
| Title: | Mutated CCDC51 coding for a mitochondrial protein, MITOK is a candidate gene defect for autosomal recessive rod-cone dystrophy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/ijms22157875 |
| Publisher version: | http://dx.doi.org/10.3390/ijms22157875 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | rod-cone dystrophy; retinitis pigmentosa; candidate gene; CCDC51; MITOK; mitochondrial protein; inner segments; retina |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10132811 |
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