Department of ophthalmology, Ain Shams University, Cairo, Egypt.
Watany Eye Hospital, Cairo, Egypt.
Ophthalmic Genet. 2023 Jun;44(3):226-233. doi: 10.1080/13816810.2023.2183223. Epub 2023 Mar 1.
Harel-Yoon syndrome (HAYOS) is a recently described neurodevelopmental disorder characterized by psychomotor delay, truncal hypotonia, appendicular spasticity, and peripheral neuropathy. It is caused by mutations in ATAD3A gene located on chromosome 1p.36.33 whose functions include mitochondrial DNA stabilization, the regulation of mitochondrial fission/fusion, and cholesterol homeostasis.
An 11-year-old male patient of consanguineous Egyptian parents, who present with neuroregression and ptosis along with progressive impaired vision, undergoes complete ophthalmological and neurological examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of both the macula and optic nerve head, full field electroretinogram (ERG), and visual field perimetry were obtained. Whole-exome sequencing and mitochondrial genome sequencing were done in a commercial laboratory from a peripheral blood sample.
A novel mutation in ATAD3A gene c.624_644del was identified by whole-exome sequencing consistent with a diagnosis of Harel-Yoon Syndrome (HAYOS). The 11-year-old boy had characteristic features of neurodevelopmental delay, hypotonia, and peripheral neuropathy. However, we documented some novel features as fatiguable ptosis, facial weakness, progressive bulbar palsy, obsessive-compulsive disorder (OCD) in addition to cone system dysfunction.
Our study reports a novel mutation in ATAD3A gene and expands the clinical spectrum of Harel-Yoon Syndrome. Future research aiming at better understanding of gene function will lead to better genotype-phenotype correlation and could pave the way to more treatment options.
Harel-Yoon 综合征（HAYOS）是一种新近描述的神经发育障碍，其特征为精神运动迟缓、躯干张力减退、四肢痉挛性瘫痪和周围神经病。它由位于 1p.36.33 染色体上的 ATAD3A 基因突变引起，该基因的功能包括线粒体 DNA 稳定、线粒体裂变/融合的调节以及胆固醇稳态。
一对近亲埃及裔父母的 11 岁男孩，表现为神经退行性和上睑下垂，伴有进行性视力受损，接受了全面的眼科和神经科检查。此外，进行了彩色眼底照相、眼底自发荧光（FAF）、黄斑和视神经头的谱域光相干断层扫描（SD-OCT）、全视野视网膜电图（ERG）和视野检查。从外周血样本在商业实验室进行了全外显子组测序和线粒体基因组测序。
通过全外显子组测序发现 ATAD3A 基因 c.624_644del 的新突变，符合 Harel-Yoon 综合征（HAYOS）的诊断。这个 11 岁的男孩具有神经发育迟缓、张力减退和周围神经病的特征。然而，我们记录了一些新的特征，如疲劳性上睑下垂、面部无力、进行性球麻痹、强迫症（OCD）以及视锥系统功能障碍。
我们的研究报告了 ATAD3A 基因的新突变，并扩展了 Harel-Yoon 综合征的临床谱。旨在更好地了解基因功能的未来研究将导致更好的基因型-表型相关性，并为更多的治疗选择铺平道路。
