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. 2025 Sep 18;18(9):1705-1712.
doi: 10.18240/ijo.2025.09.12. eCollection 2025.

Novel ATOH7 mutation and structural characterization in families with optic nerve hypoplasia

Muhammad Ikram Ullah  1 , Rubina Dad  2 , Zaira Rehman  3 , Muhammad Shakil  4   5 , Abdullah Alsrhani  1 , Ayman Ali Mohammed Alameen  1 , Heba Bassiony Ghanem  1 , Emad Manni  1 , Muhammad Umer Khan  6 , Muhammad Atif  1
Affiliations

Novel ATOH7 mutation and structural characterization in families with optic nerve hypoplasia

Muhammad Ikram Ullah et al. Int J Ophthalmol. .

Abstract

Aim: To detect and segregate causative mutations in congenital families with optic nerve hypoplasia (ONH).

Methods: Two unrelated consanguineous Pakistani families with severe ONH, showing features of micropthalmia, nystagmus, corneal opacity, and keratopathy were included. Genetic analysis was carried out by Target Panel Sequencing, and the nucleotide variant was confirmed by Sanger sequencing. In silico analyses were carried out to study the protein order-disorder functions and their effects on messenger ribonucleic acid (mRNA).

Results: Target panel sequencing revealed that the afflicted family members carried a novel frameshift mutation (NM_145178.4; c.91del G; p.Gly31Glyfs*55) that ensued in the conservation of an amino acid residue in the bHLH domain of ATOH7 protein. In silico studies predicted that the activity of the ATOH7 gene is probably affected by this mutation, which results in a shortened and non-functional protein. Three-dimensional structural analysis shows that DNA binding may be impacted by amino acid changes from non-polar to positively charged and vice versa (Arg42Pro and Pro18Arg), as well as from positively charged (Arg) to a small polar amino acid (Gly).

Conclusion: A novel ATOH7 mutation is harmful. This study also emphasizes the potential effects of modified ATOH7 configurations on the stability and functionality of proteins.

Keywords: ATOH7 gene; congenital families; disorder protein; novel mutation; optic nerve hypoplasia; structural analysis.

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Conflict of interest statement

Conflicts of Interest: Ullah MI, None; Dad R, None; Rehman Z, None; Shakil M, None; Alsrhani A, None; Alameen AAM, None; Ghanem HB, None; Manni E, None; Khan MU, None; Atif M, None.

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