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Published on: January 12, 2024
The Clinical Spectrum and Disease Course of DRAM2 Retinopathy
Tjaša Krašovec1, Marija Volk2, Maja Šuštar Habjan1
1Eye Hospital, University Medical Centre Ljubljana, Grablovičeva ulica 46, 1000 Ljubljana, Slovenia.
Abstract:
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone-rod or rod-cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.
Insights
Pathogenic variants in the DNA-damage regulated autophagy modulator 2 (DRAM2) gene cause rare retinal dystrophy. This study details two new patients and reviews 23 others, clarifying disease course and presentation.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Pathogenic variants in the DNA-damage regulated autophagy modulator 2 (DRAM2) gene are linked to a rare, autosomal recessive retinal dystrophy.
- The precise clinical course and phenotypic variability of DRAM2 retinopathy remain incompletely understood.
Purpose of the Study:
- To characterize the disease course of DRAM2 retinopathy by presenting two novel patient cases.
- To consolidate and analyze clinical data from previously reported patients with DRAM2 retinopathy.
Main Methods:
- Whole exome and whole genome sequencing were performed on two patients.
- Ophthalmological examinations with a 2-year follow-up were conducted.
- A comprehensive literature search of PubMed was performed for clinical descriptions of DRAM2 retinopathy.
Main Results:
- Two Slovenian patients with novel DRAM2 variants were identified, exhibiting distinct presentations and ages of onset.
- Review of 23 previously reported patients revealed common features: onset in the third decade, central vision loss, outer retinal thinning, and specific electroretinography patterns.
- Non-null variants were associated with milder disease phenotypes.
Conclusions:
- DRAM2 retinopathy presents with variable phenotypes, emphasizing the gene's crucial role in photoreceptor function.
- Early identification and comprehensive genetic analysis are vital for understanding and managing DRAM2-associated retinal dystrophies.
- Further research is warranted to elucidate the molecular mechanisms underlying DRAM2 retinopathy and explore potential therapeutic strategies.
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