A novel frameshift variant in LAMP2 gene mimicking choroideremia carrier retinopathy.

Autor:	Narayan A; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Taylor LJ; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK., Sperring S; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Shanks M; Oxford Regional Genetics Laboratory, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Clouston P; Oxford Regional Genetics Laboratory, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., MacLaren RE; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK., Cehajic-Kapetanovic J; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.
Jazyk:	angličtina
Zdroj:	Ophthalmic genetics [Ophthalmic Genet] 2024 Dec; Vol. 45 (6), pp. 668-675. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1080/13816810.2024.2404148
Abstrakt:	Background: Danon disease is a rare, multisystemic X-linked dominant disorder caused by variants in the LAMP2 gene. It can be associated with retinal degeneration, but this is not well characterized. Here we describe a late presentation of a mild retinal phenotype, initially diagnosed as choroideremia carrier, associated with a novel variant in the LAMP2 gene. Methods: Retrospective analysis of the case included medical history, ophthalmic examination, multimodal retinal imaging, and microperimetry. Genetic testing was conducted to establish the molecular diagnosis. Results: A 54-year-old female presented with worsening night vision, without any family history. BCVA was 6/6 bilaterally and fundus examination showed light peripheral pigmentary changes bilaterally. FAF demonstrated a widespread speckled pattern and OCT revealed hyper-reflective spots in the outer nuclear layer. Differentials included non-genetic and genetic causes, suspected of being a manifesting choroideremia carrier. However, initial genetic testing by targeted analysis of retinal disorders did not detect a pathogenic variant. Further systems review revealed that the patient had previously been diagnosed with dilated cardiomyopathy, mini-stroke and partial deafness. Subsequent whole mitochondrial genome sequencing analysis did not detect any pathogenic variants too. Finally, whole exome sequencing with targeted analysis of a panel of hypertrophic cardiomyopathy genes identified a novel pathogenic heterozygous variant (c.925del, p.(Ser309fs)) in the LAMP2 gene, confirming the diagnosis of X-linked Danon disease. Conclusion: Recording previous medical history and extraocular symptoms is crucial. The similarity in choroideremia carrier and Danon disease retinal phenotypes suggests a possible common pathway in these two genes where pathogenic variants lead to retinal pigment epithelium degeneration.
Databáze:	MEDLINE
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