Harel Yoon syndrome: a novel mutation in ATAD3A gene and expansion of the clinical spectrum

ABSTRACT

Background

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.

Materials and Methods

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.

Results

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.

Conclusion

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.

KEYWORDS:

• ATAD3A
• Harel-Yoon syndrome
• mitochondria
• novel mutation
• whole exome sequencing

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2023.2183223.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.