Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells
Acta Neuropathol Commun. 2025 Feb 13;13(1):28. doi: 10.1186/s40478-025-01942-z. ABSTRACT Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterised by the selective loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, which encodes a dynamin-related GTPase protein. OPA1 plays a key role […]
Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases
Adv Exp Med Biol. 2025;1468:89-93. doi: 10.1007/978-3-031-76550-6_15. ABSTRACT This study describes worldwide gene therapy clinical trials aimed at treating inherited retinal diseases (IRD). The information was collected through 15 different international registries including clinicaltrials.gov . There have been 101 gene therapy clinical trials targeting IRD up until the end of 2022. Seventy-seven trials employed gene […]
The Heterozygous p.A684V Variant in the WFS1 Gene Is a Mutational Hotspot Causing a Severe Hearing Loss Phenotype
Genes (Basel). 2025 Jan 6;16(1):57. doi: 10.3390/genes16010057. ABSTRACT BACKGROUND/OBJECTIVES: A heterozygous mutation in the WFS1 gene is responsible for autosomal dominant non-syndromic hearing loss (DFNA6/14/38) and Wolfram-like syndrome, which is characterized by bilateral sensorineural hearing loss with optic atrophy and/or diabetes mellitus. However, detailed clinical features for the patients with the heterozygous p.A684V variant remain […]
Derivation and Characterization of Isogenic OPA1 Mutant and Control Human Pluripotent Stem Cell Lines
Cells. 2025 Jan 17;14(2):137. doi: 10.3390/cells14020137. ABSTRACT Dominant optic atrophy (DOA) is the most commonly inherited optic neuropathy. The majority of DOA is caused by mutations in the OPA1 gene, which encodes a dynamin-related GTPase located to the mitochondrion. OPA1 has been shown to regulate mitochondrial dynamics and promote fusion. Within the mitochondrion, proteolytically processed […]
Unraveling the genetic spectrum of inherited deaf-blindness in Portugal
Orphanet J Rare Dis. 2025 Jan 14;20(1):22. doi: 10.1186/s13023-025-03542-5. ABSTRACT BACKGROUND: Syndromic genetic disorders affecting vision can also cause hearing loss, and Usher syndrome is by far the most common etiology. However, many other conditions can present dual sensory impairment. Accurate diagnosis is essential for providing patients with genetic counseling, prognostic information, and appropriate resources. […]
Angioid streaks in hereditary spherocytosis associated with an SPTB gene variant
Doc Ophthalmol. 2025 Dec;151(3):255-261. doi: 10.1007/s10633-025-10039-w. Epub 2025 Jul 9. ABSTRACT PURPOSE: To report a case of hereditary spherocytosis (HS) carrying a pathogenic variant in the SPTB gene, presenting with angioid streaks (ASs) and central retinal dysfunction. METHODS: A 63-year-old female patient diagnosed with HS was evaluated using multimodal imaging, full-field and multifocal electroretinograms (ffERGs […]
A new variant in the UCHL1 gene supporting its implication in late-onset ataxia with optic atrophy
Neurol Sci. 2025 Dec 17;47(1):11. doi: 10.1007/s10072-025-08657-y. ABSTRACT BACKGROUND: UCHL1 encodes the neuronal protein UCH-L1, which plays a critical role in protein turnover Day (Prog Neurobiol 90(3):327-362, 2010). Variants in UCHL1 have been implicated in neurodegenerative disorders and hereditary spastic paraplegia (HSP) Mi (Ageing Res Rev 6:101856, 2023); Choi et al. (J Biol Chem 279(13):13256-64, […]
A novel NR2F1-associated microdeletion underlying Bosch-Boonstra-Schaaf optic atrophy syndrome
Ophthalmic Genet. 2025 Dec;46(6):671-674. doi: 10.1080/13816810.2025.2522365. Epub 2025 Jun 26. ABSTRACT BACKGROUND: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant neurodevelopmental disorder that typically presents in early childhood. It is characterized by intellectual disability, developmental delay, and visual impairment, with optic atrophy being the most prominent ophthalmologic feature. The nuclear receptor subfamily 2, […]
Pharmacologic Inhibition of YAP/TEAD and Development of New Chorioretinal Atrophy
JAMA Ophthalmol. 2025 Dec 4:e254213. doi: 10.1001/jamaophthalmol.2025.4213. Online ahead of print. ABSTRACT IMPORTANCE: As new chemotherapy agents emerge, ophthalmologists may play a role in identifying vision-threatening adverse effects. Inherited retinal degenerations can offer insight into the changes that may result from pharmacologic inhibition of the signaling pathways involved in these conditions. OBJECTIVE: To present a […]
The Neuro-Ophthalmologic Manifestations of SPG7-Associated Disease
J Pers Med. 2025 Oct 16;15(10):495. doi: 10.3390/jpm15100495. ABSTRACT The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg weakness and spasticity) […]