Objectives

To systematically analyse the NMNAT1 variant spectrum and frequency, the associated phenotypic characteristics, and potential genotype-phenotype correlations based on our data and literature review.

Methods

Biallelic potential pathogenic variants (PPV) in NMNAT1 were collected from our in-house exome sequencing data. Whole-genome sequencing was conducted subsequently for patients with only one heterozygous PPV detected in NMNAT1. The clinical data were reviewed and evaluated in detail. Furthermore, the literature was reviewed for reports of NMNAT1 variants and their associated phenotypes.

Results

Eleven NMNAT1 variants, including two novel variants, were detected in 8 families from our cohort. All of the 9 available patients showed generalized tapetoretinal dystrophy at an early age (88.9% in the first decade), and disciform macular atrophy was identified in six patients from five unrelated families. Among a total of 125 patients from 8 families of our cohort and 91 families reported by the available literature, 92.9% patients showed onset of disease in the first year after birth, and 89.0% patients showed visual acuity of 0.05 or lower. All of the 39 patients with fundus photos available presented disciform macular atrophy with generalized tapetoretinal dystrophy. Most (54/80, 67.5%) of causative NMNAT1 variants were missense. The most frequent variants in Caucasian and Asian population are p.E257K and p.R237C, respectively.

Conclusions

Early-onset age, disciform macular atrophy with generalized tapetoretinal dystrophy, and poor visual acuity are the typical features of NMNAT1-associated retinal degeneration. Different variant hot spots of NMNAT1 were observed in different populations.

中文翻译：

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NMNAT1相关视网膜变性的临床特征和遗传谱

 目标

为了系统地分析神经网络地址转换1基于我们的数据和文献综述的变异谱和频率、相关的表型特征以及潜在的基因型-表型相关性。

 方法

双等位基因潜在致病变异（PPV）神经网络地址转换1从我们内部的外显子组测序数据中收集。随后对仅检测到一种杂合 PPV 的患者进行了全基因组测序。神经网络地址转换1 。对临床数据进行了详细审查和评估。此外，还回顾了文献中的报道神经网络地址转换1变体及其相关的表型。

 结果

十一神经网络地址转换1在我们队列的 8 个家庭中检测到了变异，包括两种新变异。所有 9 名患者均在早年表现出广泛性绦虫视网膜营养不良（88.9% 在第一个十年），来自 5 个不相关家庭的 6 名患者发现盘状黄斑萎缩。在我们队列中的8个家庭和现有文献报道的91个家庭的总共125名患者中，92.9%的患者在出生后第一年发病，89.0%的患者视力为0.05或更低。所有有眼底照片的 39 名患者均表现为盘状黄斑萎缩并伴有广泛性绦虫视网膜营养不良。大多数 (54/80, 67.5%) 的致病原因神经网络地址转换1变体是错义的。白种人和亚洲人群中最常见的变异分别是 p.E257K 和 p.R237C。

 结论

早发年龄、盘状黄斑萎缩伴广泛性视网膜营养不良和视力差是该病的典型特征神经网络地址转换1 -相关的视网膜变性。不同变体热点神经网络地址转换1在不同人群中观察到。