Variables in the ACBD5 gene leading to distinct phenotypes: A case report.
Open accessAbstract
We report the cases of a father and his daughter, the former diagnosed with retinitis pigmentosa (RP) and the latter with early foveal atrophy; while both shared a novel variant of uncertain significance (VUS) in the ACBD5 gene (variant c.431G>A), they exhibited different clinical profiles and disease manifestations. The father was a 48-year-old man who presented with nyctalopia that had persisted since age seven. He had mild disk pallor, vessel attenuation, retinal pigment epithelium (RPE) changes nasal to the fovea, and few mid-peripheral bone spicules. Sequencing analysis showed that he carried seven VUS in five genes: ACBD5 c.431G>A (p.Gly144Asp), CYP4V2 c.296T>C (p.Met99Thr), EYS c.1852G>A (p.Gly618Ser), HMCN1 c.280G>A (p.Val94Met), HMCN1 c.8939A>C (p.Asn2980Thr), RP1L1 c.575C>A (p.Pro192His), and RP1L1 c.1375A>C (p.Thr459Pro). He shared only the ACBD5 gene with his 18-year-old daughter. The daughter had 20/20 visual acuity, but further testing showed foveal atrophy and hyperautofluorescence. Intrafamilial phenotypic heterogeneity was detected in our patients. Studies on the role of hormonal factors leading to phenotypic variability are warranted.
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Two patients harbor a heterozygous c.431G>A (p.Gly144Asp) point mutation in ACBD5 and exhibit a significantly milder clinical course with solely ophthalmological symptoms.
“these two heterozygous patients exhibited a significantly milder clinical course, presenting solely with ophthalmological symptoms”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Pappaterra-Rodriguez et al., 2022
The Case presentation identifies the same heterozygous ACBD5 c.431G>A (p.Gly144Asp) variant in the father and daughter and describes ophthalmological findings in both. The Discussion says their phenotypes differed, but it does not characterize both patients’ clinical courses as significantly milder; the father had rod-cone dystrophy with severe peripheral visual-field constriction. (LLM, conf=0.82)
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Research works printed but not linked: 18
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Kors, S., Schuster, M., Maddison, D. C., Kilaru, S., Schrader, T. A., Costello, J. L., Islinger, M., Smith, G. A., & Schrader, M. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119843 · Cited by 12 · see citing works
Rudaks, L. I., Triplett, J., Morris, K., Reddel, S., & Worgan, L. (2024) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63433 · Cited by 7 · see citing works
“Both reported individuals were found to have a heterozygous variant of uncertain significance in ACBD5 with clinical features of rod-cone dystrophy and foveal atrophy, respectively (Pappaterra-Rodriguez et al., 2022).”
BackgroundThe neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models
Dawes, M. L., Haberlander, J. P., Islinger, M., & Schrader, M. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1602343 · Cited by 7 · see citing works
- Authors
- Pappaterra-Rodriguez, M. C., Muns, S. M., Ayala Rodríguez, S. C., Requejo Figueroa, G. A., Izquierdo, N., & Oliver, A. L.
- Affiliations
- University of Puerto Rico, Medical Sciences Campus (PR)
- Corresponding author
- Oliver, Armando L
- Venue
- Cureus
- Published
- 2022-12-25
- Volume
- 14
- Issue
- 12
- Pages
- e32930-e32930
- ISSN
- 2168-8184 (ISSN-L)
- PMC
- PMC9872965
- OpenAlex
- W4313202057
- Cited by
- 5
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Cureus (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- retinitis pigmentosa, variants of uncertain significance, phenotypic heterogeneity, familial inheritance, night blindness, CYP4V2, EYS, HMCN1, RP1L1, genotype-phenotype correlation, hormonal factors
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