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Rare mutations in ATL3, SPTLC2 and SCN9A explaining hereditary sensory neuropathy and congenital insensitivity to pain in a Brazilian cohort.
Cintra, Vivian Pedigone; Dohrn, Maike F; Tomaselli, Pedro José; Figueiredo, Fernanda Barbosa; Marques, Sandra Elisabete; Camargos, Sarah Teixeira; Barbosa, Luiz Sergio Mageste; P Rebelo, Adriana; Abreu, Lisa; Danzi, Matt; Marques, Wilson; Züchner, Stephan.
Afiliação
  • Cintra VP; Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA.
  • Dohrn MF; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA; Department of Neurology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Tomaselli PJ; Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Figueiredo FB; Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Marques SE; Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Camargos ST; Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Barbosa LSM; Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • P Rebelo A; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA.
  • Abreu L; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA.
  • Danzi M; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA.
  • Marques W; Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: wmjunior@fmrp.usp.br.
  • Züchner S; Dr John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, USA. Electronic address: szuchner@med.miami.edu.
J Neurol Sci ; 427: 117498, 2021 Aug 15.
Article em En | MEDLINE | ID: mdl-34090020
Hereditary sensory neuropathies (HSN) are a group of rare neurological disorders with heterogeneous clinical and genetic characteristics. Although at least 17 different genes have already been associated with HSN, the epidemiology of the disorder in Brazil is still unknown. Performing whole genome sequencing (WGS) in 23 unrelated Brazilian families diagnosed with HSN, we detected pathogenic variants in ATL3, SPTLC2, and SCN9A in 12 patients belonging to five unrelated families. Clinical features associated with heterozygous mutations in ATL3 (c.575A > G; p.(Tyr192Cys)) and SPTLC2 (c.529A > G; p.(Asn177Asp)) were sensory deficits, neuropathic pain, and recurrent ulcerations. Presenting as congenital insensitivity to pain, three unrelated probands carried biallelic loss-of-function mutations in SCN9A. The so far undescribed stop mutation c.2106G > A (p.(Trp702Ter)) and the likewise novel splicing variant c.3319-1G > A were found in compound-heterozygosity with, respectively, the known pathogenic variants c.2908G > T (p.Trp970Ter) and c.2690G > A (p.Glu897Ter). In total, we identified pathogenic mutations in 21.7% of our families, which suggests that most of the cases could be explained by yet to be discovered genes or unusual alleles. Our study represents the first mutational screen in a Brazilian HSN cohort, enabling additional insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropatias Hereditárias Sensoriais e Autônomas / Insensibilidade Congênita à Dor Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropatias Hereditárias Sensoriais e Autônomas / Insensibilidade Congênita à Dor Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda