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Pathophysiological insights into ACO2-related inherited disorders through combined functional and multi-omic analyses of ACO2 patient-derived fibroblasts

GSE332997 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2026/07/29 Platform GPL21697
At a glance

RNA-seq (gene expression) · human · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
24 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
ACO2 encodes the mitochondrial aconitase, involved in the second step of the tricarboxylic acid cycle. ACO2 variants cause isolated dominant or recessive optic atrophy, characterized by the degeneration of the optic nerves and leading to vision loss with high clinical heterogeneity, which ranges from pauci-symptomatic to legally blind patients.
Read the full summary ↓
ACO2 variants also cause rare severe syndromic presentations, like infantile cerebellar-retinal degeneration, characterized by developmental delay, truncal hypotonia, ataxia, seizures, optic atrophy and retinal degeneration. As ACO2 pathophysiology still lacks proper characterization and no treatment is available for ACO2-related disorders, we combined a functional study with a multi-omic analysis of patient-derived fibroblasts carrying ACO2 variants. Here, we show that ACO2 variants decrease ACO2 protein levels, ACO2 and cytoplasmic ACO1 mRNA expression and mtDNA levels. Metabolomic analyses identified 14 discriminating metabolites involved in amino acid metabolism, TCA cycle, nucleotide and lipid metabolism. Transcriptomic analyses disclosed a down-regulation of immunity-related pathways and an up-regulation of cell cycle-related pathways. These results provide new insights into the cellular impact of ACO2 deficiency beyond its primary role in the TCA cycle, and identify citrate accumulation as a crucial determinant in ACO2 physiopathology.
This dataset
Open GSE332997 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE332997_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1469605 and SRA study SRP703075. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in triplicate
Dominant Optic Atrophy, biol ×3 Recessive Optic Atrophy, biol ×3 Infantile Cerebellar-Retinal Degeneration, pa… ×3 Infantile Cerebellar-Retinal Degeneration, pa… ×3 Control 1, biol ×3 Control 2, biol ×3 Control 3, biol ×3 Control 4, biol ×3

Supports a case/control comparison: 6 samples read as cases, 12 as controls.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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