Expanding the phenotypic spectrum of CLCN2 -related leucoencephalopathy and ataxia.

Autor: Nóbrega PR; Division of Neurology, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil.; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil., R B de Paiva A; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.; Mendelics Genomic Analysis, Sao Paulo, Sao Paulo 02511-000, Brazil.; Department of Neurology, São Rafael Hospital, Rede D'Or São Luiz, Salvador, Bahia 41253-190, Brazil., Souza KS; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil., de Souza JLB; Center of Health Science, State University of Ceara, Fortaleza, Ceara 3101-9795, Brazil., G S B Lima PL; Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil., da Silva DJ; Universidade Federal de Goias, Goiania, Goias 74690-900, Brazil., Pitombeira MS; Hospital Geral de Fortaleza, Fortaleza, Ceara 60150-160, Brazil.; Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil., Borges VK; Hospital de Clínicas, Universidade Federal de Uberlândia, Uberlandia, Minas Gerais 38405-320, Brazil., Dias DA; Division of Radiology, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil., Bispo LM; Mendelics Genomic Analysis, Sao Paulo, Sao Paulo 02511-000, Brazil.; University Hospital, EBSERH/Federal University of Sergipe, Aracaju, Sergipe 49060-676, Brazil., Santos CF; Universidade de Fortaleza, Fortaleza, Ceara 60811-905, Brazil.; Hospital Infantil Albert Sabin, Fortaleza, Ceara 60410-794, Brazil., Freua F; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil., Silva PDS; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil., Alves IS; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil., Portella LB; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil., Cunha PR; Paris Brain Institute (ICM), Paris 75013, France., Salomao RPA; Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil., Pedroso JL; Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil., Miyajima VP; Centre for Clinical Diagnostics, Haematology and Haemotherapy Centre of Ceara (HEMOCE), Fortaleza, Ceara 60416-130, Brazil.; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK., Miyajima F; Analytical Competence Molecular Epidemiology Lab (ACME), Oswaldo Cruz Foundation (Fiocruz), Fortaleza, Ceara 61773-270, Brazil.; Postgraduate Program in Medical Sciences, Federal University of Ceará (UFC), Fortaleza, Ceara 60020-181, Brazil., Cali E; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK., Wade C; Queen Square MS Centre, UCL Institute of Neurology, London WC1N 3BG, UK., Sudarsanam A; Birmingham Children's Hospital, Birmingham, Birmingham B4 6NH, UK., O'Driscoll M; West Midlands Regional Clinical Genetics Service, Birmingham Health Partners, Birmingham Women's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK., Hayton T; University Hospital Birmingham, Birmingham B15 2GW, UK., Barsottini OGP; Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil., Klebe S; Department of Neurology, University of Würzburg, Essen 97080, Germany., Kok F; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.; Mendelics Genomic Analysis, Sao Paulo, Sao Paulo 02511-000, Brazil., Lucato LT; Neuroradiology Section, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo,Sao Paulo, Sao Paulo 05403-010, Brazil.; Grupo Fleury, São Paulo, São Paulo 01333-011, Brazil., Houlden H; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.; National Hospital for Neurology & Neurosurgery, London WC1N 3BG, UK., Depienne C; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen 45147, Germany., Lynch DS; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.; National Hospital for Neurology & Neurosurgery, London WC1N 3BG, UK., Braga-Neto P; Division of Neurology, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil.; Center of Health Science, State University of Ceara, Fortaleza, Ceara 3101-9795, Brazil.; Postgraduate Program in Medical Sciences, Federal University of Ceará (UFC), Fortaleza, Ceara 60020-181, Brazil.
Jazyk: angličtina
Zdroj: Brain communications [Brain Commun] 2023 Oct 17; Vol. 6 (1), pp. fcad273. Date of Electronic Publication: 2023 Oct 17 (Print Publication: 2024).
DOI: 10.1093/braincomms/fcad273
Abstrakt: Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T 2 -weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2 -related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2 -related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.
Competing Interests: The corresponding author declares on behalf of all authors that there are no competing interests.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze: MEDLINE
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