Abdelkader Ehab, Brandau Oliver, Bergmann Carsten, AlSalamah Nuha, Nowilaty Sawsan, Schatz Patrik
a Ophthalmology Department , Royal Alexandra Hospital , Paisley , UK.
b Ophthalmology Department , Menoufia University , Shebin El-Kom , Egypt.
Ophthalmic Genet. 2018 Dec;39(6):678-683. doi: 10.1080/13816810.2018.1522653. Epub 2018 Oct 5.
To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM).
Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS).
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.
These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.
报告7个无关近亲性色盲（ACHM）家族中的5种新的基因变异。
对患者进行多模态视网膜成像和全视野视网膜电图（ffERG）检查。使用下一代测序（NGS）进行基因检测。
在CNGA3中检测到3种新的纯合变异：外显子8中检测到一个错义c.967G>C（p.Ala323Pro）变异（1例患者），内含子2中一个剪接位点变异c.101+1G>A（3例患者），以及内含子4中一个剪接位点变异c.395+1G>T（1例患者）。在PDE6C中发现另外2种新变异：外显子15中一个纯合错义变异c.1899C>A（p.His633Gln）（1例患者）和内含子7中一个纯合剪接位点变异c.1072-1G>C（1例患者）。7个家族中的3个家族可以进行突变分离评估。所有患者的ffERG 30Hz闪烁反应均不可记录，单闪光锥体反应降低，但杆体反应保留。患者表现出不同程度的黄斑外层视网膜层缺失和黄斑高自发荧光的不同模式。
这些新变异扩展了与ACHM相关的基因型，可能有助于未来ACHM治疗的发展。
