Novel causative variants in patients with achromatopsia |
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| Authors: | Ehab Abdelkader Oliver Brandau Carsten Bergmann Nuha AlSalamah Sawsan Nowilaty |
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| Affiliation: | 1. Ophthalmology Department, Royal Alexandra Hospital, Paisley, UK;2. Ophthalmology Department, Menoufia University, Shebin El-Kom, Egypt;3. Bioscientia Center for Human Genetics, Ingelheim, Germany;4. King Saud University Hospital, Riyadh, Kingdom of Saudi Arabia;5. King Khaled Eye Specialist Hospital, Vitreoretinal Division, Riyadh, Saudi Arabia |
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| Abstract: | ABSTRACTPurpose: To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM).Methods: Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS).Results: Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence.Conclusions: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM. |
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| Keywords: | Achromatopsia CNGA3 variant cone dysfunction electroretinogram fundus autofluorescence PDE6C variant |
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