Neurol Genet
From the Department of Neurology (A.V., M.V.P., D.S.); Department of Clinical Genomics (L.A.S.); Division of Pediatric Pulmonology (N.D., R.P.B.), Department of Pediatrics and Adolescent Medicine; Division of Pediatric Rehabilitation Medicine, Department of Physical Medicine and Rehabilitation (A.E.R.); and Department of Pediatrics and Adolescent Medicine (C.R.F.), Mayo Clinic.
Published: December 2024
Objectives: Apoptosis-inducing factor mitochondria-associated 1 () gene encodes a mitochondrial flavoprotein that mediates caspase-independent programmed cell death. We report a novel AIFM1 variant in 2 siblings with early-onset hearing loss and progressive cerebellar ataxia.
Methods: We evaluated the clinical features, brain MRI scans, EMG studies, and whole genome sequencing (WGS).
Results: Sibling A is a 19-year-old man with auditory neuropathy at age 15 years, who subsequently developed optic atrophy, progressive gait and limb ataxia, peripheral neuropathy, and ambulation with cane by age 17 years. Brain MRI was normal. Sibling B is a 13-year-old boy with auditory neuropathy diagnosed at 7 and gait instability at 13, with rapid development of peripheral neuropathy, cerebellar ataxia, muscle weakness and atrophy needing wheelchair for mobility, and neuromuscular respiratory failure requiring noninvasive ventilation. Brain MRI showed mild cerebellar atrophy. Initial EMGs showed axonal neuropathy in both and diffuse chronic and active anterior horn cell disorder later in Sibling B. WGS revealed an X-linked, maternally inherited novel variant (c.1299C>G p. Ile433Met).
Discussion: AIFM1 variants should be considered in patients with hereditary cerebellar ataxia and auditory neuropathy. We highlight a novel AIFM1 variant and its phenotypic intrafamilial variability expanding the knowledge of the genetic spectrum of AIFM1-related diseases.
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http://dx.doi.org/10.1212/NXG.0000000000200216 | DOI Listing |
Cureus
December 2024
Department of Neurology, St. Joseph Medical Center, Stockton, USA.
Cerebellar mutism syndrome (also known as posterior fossa syndrome) has been mostly seen in pediatric patients after surgery for neoplastic disease and is characterized by mutism, with variable symptoms such as emotional lability, ataxia, apraxia, and hypotonia. While the mechanism is not precisely defined, it is thought to result from disconnections between the cortical and cerebellar brain networks. Presentation in adult patients is rare, with various etiologies including posterior fossa ischemia, hemorrhage, and tumors being most reported.
View Article and Find Full Text PDFIntroduction: COQ4 mutation often leads to a fatal multi-system disease in infants. Recently, it was reported that the biallelic COQ4 variants may be a potential cause of hereditary spastic paraplegia (HSP). This study aims to describe the clinical features and genotype of the COQ4 associated hereditary spastic paraplegia (HSP).
View Article and Find Full Text PDFJ Neuroophthalmol
January 2025
Departments of Ophthalmology and Visual Sciences (HMM, AH, EM), and Radiology (DMM), University of Toronto, Toronto, Canada; Department of Ophthalmology (LD), McMaster University, Hamilton, Canada; Departments of Ophthalmology and Visual Sciences, and Neurology (JDT), University of Michigan, Ann Arbor, Michigan; Department of Neurology (JDT), University of Michigan, Ann Arbor, Michigan; Division of Neurology, Department of Medicine (EM), University of Toronto, Toronto, Canada.
Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare and poorly understood inflammatory disorder of the central nervous system centered on the pons. It has a characteristic imaging appearance with enhancing and T2-hyperintense punctate and curvilinear lesions in the pons. The lesions lack restricted diffusion and have relatively little perilesional edema.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore St., Baltimore, MD 21201, USA.
The cerebellum, a key target of ethanol's toxic effects, is associated with ataxia following alcohol consumption. However, the impact of ethanol on Purkinje cell (PC) mitochondria remains unclear. To investigate how ethanol administration affects mitochondrial dynamics in cerebellar Purkinje cells, we employed a transgenic mouse model expressing mitochondria-targeted yellow fluorescent protein in Purkinje cells (PC-mito-eYFP).
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