Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

Autor:	Elbert A; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Dixon K; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Shen Y; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Hamilton S; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Boerkoel CF; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Jones SJ; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada., Kanungo AK; From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada.
Jazyk:	angličtina
Zdroj:	Neurology. Genetics [Neurol Genet] 2023 Dec 07; Vol. 10 (1), pp. e200114. Date of Electronic Publication: 2023 Dec 07 (Print Publication: 2024).
DOI:	10.1212/NXG.0000000000200114
Abstrakt:	Objectives: To investigate the etiology of cerebellar ataxia in an adult male patient. Methods: We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities. Results: The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms. Nerve conduction studies showed mild peripheral sensory neuropathy and normal motor nerve conduction velocities. Brain imaging showed progressive cerebellar atrophy and gliosis of the olivopontocerebellar fibers, characterized by T2 hyperintensity within the pons. Genetic testing revealed a likely pathogenic germline variant in MFN2 (NM_014874: c.[838C>T];[=], p.(R280C)) in the GTPase domain (G) interface; pathogenic variants of MFN2 typically cause hereditary sensory and motor neuropathy VI or Charcot-Marie-Tooth disease 2A. The presence of progressive ataxia, "hot cross bun" sign, and dysautonomia has been associated with multiple system atrophy, cerebellar type (MSA-C). Discussion: We describe progressive cerebellar ataxia in an individual with a deleterious variant in MFN2 . Our findings suggest that pathogenic variants in MFN2 can result in a spectrum of phenotypes including cerebellar ataxia with cerebellar-pontine atrophy in the absence of significant neuropathy and in a manner closely resembling MSA-C. Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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