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Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.
Nóbrega, Paulo R; R B de Paiva, Anderson; Souza, Katiane S; de Souza, Jorge Luiz B; G S B Lima, Pedro Lucas; da Silva, Delson José; Pitombeira, Milena Sales; Borges, Viviennee K; Dias, Daniel A; Bispo, Luciana M; Santos, Carolina F; Freua, Fernando; Silva, Paulo Diego S; Alves, Isabela S; Portella, Leonardo B; Cunha, Paulina R; Salomao, Rubens Paulo A; Pedroso, José Luiz; Miyajima, Veridiana P; Miyajima, Fábio; Cali, Elisa; Wade, Charles; Sudarsanam, Annapurna; O'Driscoll, Mary; Hayton, Tom; Barsottini, Orlando G P; Klebe, Stephan; Kok, Fernando; Lucato, Leandro Tavares; Houlden, Henry; Depienne, Christel; Lynch, David S; Braga-Neto, Pedro.
Afiliación
  • Nóbrega PR; Division of Neurology, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara 60430-160, 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.
  • Souza KS; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.
  • de Souza JLB; Mendelics Genomic Analysis, Sao Paulo, Sao Paulo 02511-000, Brazil.
  • G S B Lima PL; Department of Neurology, São Rafael Hospital, Rede D'Or São Luiz, Salvador, Bahia 41253-190, Brazil.
  • da Silva DJ; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.
  • Pitombeira MS; Center of Health Science, State University of Ceara, Fortaleza, Ceara 3101-9795, Brazil.
  • Borges VK; Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil.
  • Dias DA; Universidade Federal de Goias, Goiania, Goias 74690-900, Brazil.
  • Bispo LM; Hospital Geral de Fortaleza, Fortaleza, Ceara 60150-160, Brazil.
  • Santos CF; Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.
  • Freua F; Hospital de Clínicas, Universidade Federal de Uberlândia, Uberlandia, Minas Gerais 38405-320, Brazil.
  • Silva PDS; Division of Radiology, Federal University of Ceara, Fortaleza, Ceara 60430-160, Brazil.
  • Alves IS; Mendelics Genomic Analysis, Sao Paulo, Sao Paulo 02511-000, Brazil.
  • Portella LB; University Hospital, EBSERH/Federal University of Sergipe, Aracaju, Sergipe 49060-676, Brazil.
  • Cunha PR; Universidade de Fortaleza, Fortaleza, Ceara 60811-905, Brazil.
  • Salomao RPA; Hospital Infantil Albert Sabin, Fortaleza, Ceara 60410-794, Brazil.
  • Pedroso JL; Neurogenetics Unit, Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo 05403-000, Brazil.
  • Miyajima VP; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil.
  • Miyajima F; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil.
  • Cali E; Prevent Senior, Sao Paulo, Sao Paulo 01401-001, Brazil.
  • Wade C; Paris Brain Institute (ICM), Paris 75013, France.
  • Sudarsanam A; Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil.
  • O'Driscoll M; Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil.
  • Hayton T; Centre for Clinical Diagnostics, Haematology and Haemotherapy Centre of Ceara (HEMOCE), Fortaleza, Ceara 60416-130, Brazil.
  • Barsottini OGP; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.
  • Klebe S; Analytical Competence Molecular Epidemiology Lab (ACME), Oswaldo Cruz Foundation (Fiocruz), Fortaleza, Ceara 61773-270, Brazil.
  • Kok F; Postgraduate Program in Medical Sciences, Federal University of Ceará (UFC), Fortaleza, Ceara 60020-181, Brazil.
  • Lucato LT; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
  • Houlden H; Queen Square MS Centre, UCL Institute of Neurology, London WC1N 3BG, UK.
  • Depienne C; Birmingham Children's Hospital, Birmingham, Birmingham B4 6NH, UK.
  • Lynch DS; West Midlands Regional Clinical Genetics Service, Birmingham Health Partners, Birmingham Women's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK.
  • Braga-Neto P; University Hospital Birmingham, Birmingham B15 2GW, UK.
Brain Commun ; 6(1): fcad273, 2024.
Article en En | MEDLINE | ID: mdl-38173802
ABSTRACT
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 T2-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Brain Commun Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Brain Commun Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido