RPE65 mutations in Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa from a tertiary eye care center in India.

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-06-01 Epub Date: 2024-02-07 DOI:10.1080/13816810.2024.2309559
Deepika C Parameswarappa, Deepak Kumar Bagga, Abhishek Upadhyaya, Jeyapoorani Balasubramanian, Venkatesh Pochaboina, Vani Muthineni, Subhadra Jalali, Chitra Kannabiran
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引用次数: 0

Abstract

Introduction: Mutations in the retinal pigment epithelial 65 kilodalton protein (RPE65) gene are associated with various inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). We screened for mutations in RPE65 in a series of Indian patients with these IRDs to determine the frequency/types of mutations and to describe the associated phenotypes.

Materials and methods: Diagnosis of LCA, EOSRD, and RP was made by standard and pre-defined criteria. Patients were evaluated by clinical, retinal imaging, and electrophysiological parameters. Genomic DNA from patients and available family members were used for identifying mutations by direct Sanger sequencing of the RPE65 gene or targeted NGS gene panel for IRDs covering 260+ genes. Variations detected were tested in healthy control populations and for co-segregation with the disease in available family members.

Results: Mutations were found in eight patients, out of 220 total cases screened, all homozygous for the respective mutant alleles. Seven patients had mutations leading to premature termination codons and one patient had a missense change. The onset of visual loss ranged from birth to <2 years of life. At presentation, RPE mottling in the background retina was present in all cases with macular involvement in five cases with or without vascular attenuation and optic disc pallor.

Conclusion: RPE65 mutations in this series were found in 3.6% of cases associated with severe, early-onset disease, with consistent RPE mottling and variable manifestations with regard to the extent of disc pallor, arteriolar attenuation, and appearance of the macula.

印度一家三级眼科医疗中心的 Leber 先天性无视力症、早发严重视网膜营养不良症和视网膜色素变性症中的 RPE65 基因突变。
导言:视网膜色素上皮 65 千道尔顿蛋白(RPE65)基因突变与多种遗传性视网膜疾病(IRDs)有关,包括先天性弱视(LCA)、早发严重视网膜营养不良(EOSRD)和视网膜色素变性(RP)。我们在一系列患有这些IRD的印度患者中筛查了RPE65的突变,以确定突变的频率/类型并描述相关的表型:LCA、EOSRD和RP的诊断依据标准和预定义标准。通过临床、视网膜成像和电生理参数对患者进行评估。通过对 RPE65 基因进行直接 Sanger 测序,或对涵盖 260 多个基因的 IRDs 靶向 NGS 基因面板进行测序,确定患者和现有家庭成员的基因组 DNA 变异。在健康对照人群中检测所发现的变异,并在现有家庭成员中检测与疾病的共分离情况:结果:在筛查的 220 例患者中,有 8 例发现了基因突变,所有患者均为各自突变等位基因的同源染色体。七名患者的基因突变导致过早终止密码子,一名患者的基因突变导致错义。视力丧失的发病时间从出生到结论不等:在该系列病例中,有 3.6% 的病例发现了 RPE65 突变,这些病例伴有严重的早发性疾病,RPE 斑驳一致,在视盘苍白程度、动脉衰减和黄斑外观方面表现各异。
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来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
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