# Genetic underpinnings explored: OPA1 deletion and complex phenotypes on chromosome 3q29

## TL;DR

A patient with optic atrophy and a brain aneurysm was found to have a rare 3q29 deletion involving the OPA1 gene, highlighting the importance of detecting copy-number variations in genetic disorders.

## Contribution

This case highlights the underestimation of OPA1 deletions due to sequencing limitations and emphasizes the need for targeted CNV analysis in ADOA patients.

## Key findings

- A de novo 960 kb deletion on 3q29 encompassing OPA1 was identified in a patient with optic atrophy and a brain aneurysm.
- The optic atrophy is conclusively linked to the OPA1 deletion, but the aneurysm is likely coincidental.
- Sequencing technology limitations may lead to underdiagnosis of OPA1 deletions in Autosomal Dominant Optic Atrophy.

## Abstract

Copy number variations (CNVs) have emerged as significant contributors to the elusive genetic causality of inherited eye diseases. In this study, we describe a case with optic atrophy and a brain aneurysm, in which a de novo CNV 3q29 deletion was identified.

A 40-year-old female patient was referred to our department after undergoing aneurysm transcatheter arterial embolization for a brain aneurysm. She had no history of systemic diseases, except for unsatisfactory best-corrected visual acuity (BCVA) since elementary school. Electrophysiological tests confirmed the findings in retinal images, indicating optic nerve atrophy. Chromosomal microarray analysis revealed a de novo deletion spanning 960 kb on chromosome 3q29, encompassing OPA1 and six neighboring genes. Unlike previously reported deletions in this region associated with optic atrophy, neuropsychiatric disorders, and obesity, this patient displayed a unique combination of optic atrophy and a brain aneurysm. However, there is no causal relationship between the brain aneurysm and the CNV.

In conclusion, the optic atrophy is conclusively attributed to the OPA1 deletion, and the aneurysm could be a coincidental association. The report emphasizes the likelihood of underestimating OPA1 deletions due to sequencing technology limitations. Recognizing these constraints, healthcare professionals must acknowledge these limitations and consistently search for OPA1 variants/deletions in Autosomal Dominant Optic Atrophy (ADOA) patients with negative sequencing results. This strategic approach ensures a more comprehensive exploration of copy-number variations, ultimately enhancing diagnostic precision in the field of genetic disorders.

The online version contains supplementary material available at 10.1186/s12920-024-01850-6.