SCLT1 缺失的两个兄弟姐妹的锥体感光器功能减退和微妙的全身表现。

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-02-01 Epub Date: 2023-05-29 DOI:10.1080/13816810.2023.2215332
Monika K Grudzinska Pechhacker, Anna Molnar, Nadja Pekkola Pacheco, Håkan Thonberg, Laurence Querat, Ulrika Birkeldh, Ann Nordgren, Anna Lindstrand
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引用次数: 0

摘要

背景:钠通道和凝集素连接体 1 基因(SCLT1)与各种纤毛病的发病机制有关,如巴尔德-比德尔综合征、口角畸形综合征 IX 型和 Senior-Løken 综合征。需要进行详细检查以确定所有临床特征。在此,我们介绍一个表型较轻的SCLT1相关疾病家族:进行全面的眼部检查,包括眼底图像、OCT、色觉、视野和视网膜电图。儿科医生和医学遗传学家对受影响的个体进行了纤毛虫病系统特征评估。检查项目包括超声心动图、腹部超声波检查、糖尿病血液检查、肝功能和肾功能检查。基因检测包括 NGS 视网膜营养不良面板、分离分析和转录组测序:两名分别为10岁和8岁的男童患有注意力缺陷多动障碍(ADHD)、肥胖和轻度畏光。眼科检查显示其最佳矫正视力(BCVA)下降、斜视、远视、散光和中度红绿缺陷。视网膜造影显示光感受器病变较轻。视网膜电图证实锥体感光器功能障碍。基因检测显示,该患者和受影响的兄弟体内的SCLT1基因NM_144643.3:c.1439 + 1del存在一个可能致病的同源剪接位点变异。未受影响的父母是 SCLT1 变异的杂合子。转录组测序显示,该患者保留了内含子 16:在本报告中,我们强调了对不明原因的视力下降、斜视、屈光不正和多动症谱系障碍患者进行进一步广泛诊断的重要性。与 SCLT1 相关的视网膜变性非常罕见,以前从未观察到锥体光感受器的单独功能减退。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1.

Background: The sodium channel and clathrin linker 1 gene (SCLT1) has been involved in the pathogenesis of various ciliopathy disorders such as Bardet-Biedl syndrome, orofaciodigital syndrome type IX, and Senior-Løken syndrome. Detailed exams are warranted to outline all clinical features. Here, we present a family with a milder phenotype of SCLT1-related disease.

Material and methods: Comprehensive eye examination including fundus images, OCT, color vision, visual fields and electroretinography were performed. Affected individuals were assessed by a pediatrician and a medical geneticist for systemic features of ciliopathy. Investigations included echocardiography, abdominal ultrasonography, blood work-up for diabetes, liver and kidney function. Genetic testing included NGS retinal dystrophy panel, segregation analysis and transcriptome sequencing.

Results: Two male children, age 10 and 8 years, were affected with attention deficit hyperactivity disorder (ADHD), obesity and mild photophobia. The ophthalmic exam revealed reduced best-corrected visual acuity (BCVA), strabismus, hyperopia, astigmatism and moderate red-green defects. Milder changes suggesting photoreceptors disease were found on retinal imaging. Electroretinogram confirmed cone photoreceptors dysfunction. Genetic testing revealed a homozygous likely pathogenic, splice-site variant in SCLT1 gene NM_144643.3: c.1439 + 1del in the proband and in the affected brother. The unaffected parents were heterozygous for the SCLT1 variant. Transcriptome sequencing showed retention of intron 16 in the proband.

Conclusions: In this report, we highlight the importance of further extensive diagnostics in patients with unexplained reduced vision, strabismus, refractive errors and ADHD spectrum disorders. SCLT1-related retinal degeneration is very rare and isolated reduced function of cone photoreceptors has not previously been observed.

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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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