Expanding the phenotypic and genotypic spectrum of patients with HGSNAT-related retinopathy.

IF 1.2 4区医学 Q4 GENETICS & HEREDITY

Ophthalmic Genetics Pub Date : 2024-04-01 Epub Date: 2023-08-17 DOI:10.1080/13816810.2023.2245035

Mariana Matioli da Palma, Molly Marra, Austin D Igelman, Cristy A Ku, Amanda Burr, Katherine Andersen, Lesley A Everett, Fernanda B O Porto, Juliana Maria Ferraz Sallum, Paul Yang, Mark E Pennesi

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引用次数: 0

Abstract

Background: Variants in HGSNAT have historically been associated with syndromic mucopolysaccharidosis type IIIC (MPSIIIC) but more recent studies demonstrate cases of HGSNAT-related non-syndromic retinitis pigmentosa. We describe and expand the genotypic and phenotypic spectrum of this disease.

Materials and methods: This is a retrospective, observational, case series of 11 patients with pericentral retinitis pigmentosa due to variants in HGSNAT gene without a syndromic diagnosis of MPSIIIC. We reviewed ophthalmologic data extracted from medical records, genetic testing, color fundus photos, fundus autofluorescence (FAF), and optical coherence tomography (OCT).

Results: Of the 11 patients, the mean age was 52 years (range: 26-78). The mean age of ophthalmologic symptoms onset was 45 years (range: 15-72). The visual acuity varied from 20/20 to 20/80 (mean 20/30 median 20/20). We described five novel variants in HGSNAT: c.715del (p.Arg239Alafs *37), c.118 G>A (p.Asp40Asn), c.1218_1220delinsTAT, c.1297A>G (p.Asn433Asp), and c.1726 G>T (p.Gly576*).

Conclusions: HGSNAT has high phenotypic heterogeneity. Data from our cohort showed that all patients who had at least one variant of c.1843 G>A (p.Ala615Thr) presented with the onset of ocular symptoms after the fourth decade of life. The two patients with onset of ocular symptoms before the fourth decade did not carry this variant. This may suggest that c.1843 G>A variant is associated with a later onset of retinopathy.

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扩大 HGSNAT 相关视网膜病变患者的表型和基因型范围。

背景：HGSNAT的变异体历来与综合征性粘多糖病IIIC型（MPSIIIC）有关，但最近的研究发现了与HGSNAT相关的非综合征性色素性视网膜炎病例。我们描述并扩展了这种疾病的基因型和表型谱：这是一项回顾性、观察性、病例系列研究，共收集了 11 例因 HGSNAT 基因变异导致的中心周围视网膜色素变性患者，这些患者均未被综合诊断为 MPSIIIC。我们回顾了从病历、基因检测、彩色眼底照片、眼底自动荧光（FAF）和光学相干断层扫描（OCT）中提取的眼科数据：11 名患者的平均年龄为 52 岁（26-78 岁）。眼科症状的平均发病年龄为 45 岁（范围：15-72 岁）。视力从20/20到20/80不等（平均20/30，中位20/20）。我们描述了 HGSNAT 的五个新变异：c.715del (p.Arg239Alafs *37)、c.118 G>A (p.Asp40Asn) 、c.1218_1220delinsTAT、c.1297A>G (p.Asn433Asp) 和 c.1726 G>T (p.Gly576*)：结论：HGSNAT具有高度的表型异质性。我们的队列数据显示，所有至少有一个c.1843 G>A（p.Ala615Thr）变异的患者都是在生命的第四个十年后出现眼部症状。而在第四个十年之前出现眼部症状的两名患者则没有携带该变异体。这可能表明，c.1843 G>A 变异与视网膜病变的发病时间较晚有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.