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Dopachrome tautomerase variants in patients with oculocutaneous albinism
- Source :
- Genetics in Medicine, Genetics in Medicine, Nature Publishing Group, 2021, 23 (3), pp.479-487. ⟨10.1038/s41436-020-00997-8⟩, Pennamen, P, Tingaud-Sequeira, A, Gazova, I, Keighren, M, McKie, L, Marlin, S, Halem, S G, Kaplan, J, Delevoye, C, Lacombe, D, Plaisant, C, Michaud, V, Lasseaux, E, Javerzat, S, Jackson, I J & Arveiler, B 2021, ' Dopachrome tautomerase variants in patients with oculocutaneous albinism ', Genetics in Medicine . https://doi.org/10.1038/s41436-020-00997-8, Genetics in Medicine, 2021, 23 (3), pp.479-487. ⟨10.1038/s41436-020-00997-8⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- PurposeAlbinism is a clinically and genetically heterogeneous condition. Despite analysis of the nineteen known genes, ∼30% patients remain unsolved. We aimed to identify new genes involved in albinism.MethodsWe sequenced a panel of genes with known or predicted involvement in melanogenesis in 230 unsolved albinism patients.ResultsWe identified variants in theDopachrome tautomerase(DCT) gene in two patients. One was compound heterozygous for a 14 bp deletion in exon 9 and c.118T>A p.(Cys40Ser). The second was homozygous for c.183C>G p.(Cys61Trp). Both patients had mild hair and skin hypopigmentation, and classical ocular features. CRISPR/Cas9 was used in C57BL/6J mice to create mutations identical to the missense mutations carried by the patients, along with one loss-of-function indel mutation. When bred to homozygosity the three mutations revealed hypopigmentation of the coat, milder for Cys40Ser compared to Cys61Trp or the frameshift mutation. Histological analysis identified significant hypopigmentation of the retinal pigmented epithelium (RPE) indicating that defective RPE melanogenesis could be associated with eye and vision defects.DCTloss of function in zebrafish embryos elicited hypopigmentation both in melanocytes and RPE cells.ConclusionsDCTis the gene for a new type of oculocutaneous albinism that we propose to name OCA8.
- Subjects :
- 0301 basic medicine
Mouse
Albinism
030105 genetics & heredity
Biology
Compound heterozygosity
Frameshift mutation
Mice
03 medical and health sciences
Exon
0302 clinical medicine
medicine
Animals
Humans
Missense mutation
Genetics (clinical)
Zebrafish
030304 developmental biology
Hypopigmentation
Genetics
0303 health sciences
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Pigmentation
DCT
medicine.disease
Oculocutaneous albinism
3. Good health
Intramolecular Oxidoreductases
Mice, Inbred C57BL
030104 developmental biology
Albinism, Oculocutaneous
030220 oncology & carcinogenesis
Mutation
medicine.symptom
Dopachrome tautomerase
INDEL Mutation
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 10983600 and 15300366
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine, Genetics in Medicine, Nature Publishing Group, 2021, 23 (3), pp.479-487. ⟨10.1038/s41436-020-00997-8⟩, Pennamen, P, Tingaud-Sequeira, A, Gazova, I, Keighren, M, McKie, L, Marlin, S, Halem, S G, Kaplan, J, Delevoye, C, Lacombe, D, Plaisant, C, Michaud, V, Lasseaux, E, Javerzat, S, Jackson, I J & Arveiler, B 2021, ' Dopachrome tautomerase variants in patients with oculocutaneous albinism ', Genetics in Medicine . https://doi.org/10.1038/s41436-020-00997-8, Genetics in Medicine, 2021, 23 (3), pp.479-487. ⟨10.1038/s41436-020-00997-8⟩
- Accession number :
- edsair.doi.dedup.....49a3fe751ab686323328c7a3650c2c5f