Novel AIFM1 Variant in 2 Siblings With Sensorineural Hearing Loss and Cerebellar Ataxia.

Autor:	Vasquez A; 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., Schimmenti LA; 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., Demirel N; 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., Rabatin AE; 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., Fischer CR; 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., Pinto MV; 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., Boesch RP; 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., Selcen D; 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.
Jazyk:	angličtina
Zdroj:	Neurology. Genetics [Neurol Genet] 2024 Nov 25; Vol. 10 (6), pp. e200216. Date of Electronic Publication: 2024 Nov 25 (Print Publication: 2024).
DOI:	10.1212/NXG.0000000000200216
Abstrakt:	Objectives: Apoptosis-inducing factor mitochondria-associated 1 ( AIFM1 ) 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 AIFM1 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. Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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