Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function
FASEB J. 2025 Apr 15;39(7):e70497. doi: 10.1096/fj.202403271R. ABSTRACT Autosomal optic atrophy (AOA) is a form of hereditary optic neuropathy characterized by the irreversible and progressive degermation of the retinal ganglion cells. Most cases of AOA are associated with a single dominant mutation in OPA1, which encodes a protein required for fusion of the inner mitochondrial […]
Incidence and health burden of 20 rare neurological diseases in South China from 2016 to 2022: a hospital-based observational study
Orphanet J Rare Dis. 2025 Apr 8;20(1):163. doi: 10.1186/s13023-025-03704-5. ABSTRACT BACKGROUND: Rare neurological diseases (RNDs) result in severe health burdens worldwide. Data from China are limited. We aimed to investigate the health burden of 20 RNDs in Guangdong Province (GD), which contains two-thirds of the population of South China. METHODS: The hospitalization data of 20 […]
Natural history of patients with autosomal dominant WFS1 pathogenic variants associated with sensorineural hearing loss and optic atrophy
medRxiv [Preprint]. 2025 Feb 25:2025.02.23.25322342. doi: 10.1101/2025.02.23.25322342. ABSTRACT OBJECTIVE: Autosomal dominant pathogenic variants in the WFS1 gene can cause a broad spectrum of WFS1-related disorders. These disorders present with a range of phenotypic manifestations, including isolated low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, isolated diabetes mellitus, and […]
A novel frameshift variant leads to familial osteopetrosis with variable phenotypes in a Chinese Han consanguineous family
BMC Med Genomics. 2025 Feb 24;18(1):36. doi: 10.1186/s12920-025-02101-y. ABSTRACT Osteopetrosis, a group of highly heterogeneous genetic bone disorders, is characterized by deafness, increased bone density, hepatosplenomegaly, pancytopenia and intellectual disability. Osteopetrosis can be divided into three subtypes: autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IARO), and autosomal dominant osteopetrosis (ADO). CLCN7 has been reported […]
Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants: Insights From a Hungarian Cohort
Clin Genet. 2025 Aug;108(2):124-133. doi: 10.1111/cge.14719. Epub 2025 Feb 20. ABSTRACT Mitochondria-associated paraplegin dysfunction is primarily linked to spastic paraplegia; however, genetic alterations in SPG7 have been associated with a broader spectrum of clinical symptoms. To identify disease-causing variants in the SPG7 gene, 437 patients with spastic ataxia, mitochondrial dysfunction-associated symptoms, or motoneuron lesions detected […]
If at first you don’t succeed, try, try again
Surv Ophthalmol. 2025 Jul-Aug;70(4):840-844. doi: 10.1016/j.survophthal.2025.01.011. Epub 2025 Feb 14. ABSTRACT A previously healthy 15-year-old Asian boy presented with progressive bilateral painless vision loss, dyschromatopsia, and visual field defects. Optical coherence tomography showed diffuse retinal nerve fiber layer thinning. Work-up including neuroimaging, lab testing for acquired bilateral optic atrophy, extensive mitochondrial and nuclear genetic testing […]
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 […]