Manifesting carriers of X-linked myotubular myopathy: Genetic modifiers modulating the phenotype

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.creatorSouza, Lucas Santos-
Autor(es): dc.creatorAlmeida, Camila Freitas-
Autor(es): dc.creatorYamamoto, Guilherme Lopes-
Autor(es): dc.creatorMingroni Pavanello, Rita de Cássia-
Autor(es): dc.creatorGurgel-Giannetti, Juliana-
Autor(es): dc.creatorda Costa, Silvia Souza-
Autor(es): dc.creatorAnequini, Isabela Pessa-
Autor(es): dc.creatordo Carmo, Silvana Amanda-
Autor(es): dc.creatorTing Wang, Jaqueline Yu-
Autor(es): dc.creatorde Oliveira Scliar, Marília-
Autor(es): dc.creatorCastelli, Erick C. [UNESP]-
Autor(es): dc.creatorOtto, Paulo Alberto-
Autor(es): dc.creatorZanoteli, Edmar-
Autor(es): dc.creatorVainzof, Mariz-
Data de aceite: dc.date.accessioned2022-02-22T00:51:47Z-
Data de disponibilização: dc.date.available2022-02-22T00:51:47Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2019-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1212/NXG.0000000000000513-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/207914-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/207914-
Descrição: dc.descriptionObjective To analyze the modulation of the phenotype in manifesting carriers of recessive X-linked myotubular myopathy (XLMTM), searching for possible genetic modifiers. Methods Twelve Brazilian families with XLMTM were molecularly and clinically evaluated. In 2 families, 4 of 6 and 2 of 5 manifesting female carriers were identified. These females were studied for X chromosome inactivation. In addition, whole-exome sequencing was performed, looking for possible modifier variants. We also determined the penetrance rate among carriers of the mutations responsible for the condition. Results Mutations in the MTM1 gene were identified in all index patients from the 12 families, being 4 of them novel. In the heterozygotes, X chromosome inactivation was random in 3 of 4 informative manifesting carriers. The disease penetrance rate was estimated to be 30%, compatible with incomplete penetrance. Exome comparative analyses identified variants within a segment of 4.2 Mb on chromosome 19, containing the killer cell immunoglobulin-like receptor cluster of genes that were present in all nonmanifesting carriers and absent in all manifesting carriers. We hypothesized that these killer cell immunoglobulin-like receptor variants may modulate the phenotype, acting as a protective factor in the nonmanifesting carriers. Conclusions Affected XLMTM female carriers have been described with a surprisingly high frequency for a recessive X-linked disease, raising the question about the pattern of inheritance or the role of modifier factors acting on the disease phenotype. We demonstrated the possible existence of genetic mechanisms and variants accountable for the clinical manifestation in these women, which can become future targets for therapies.-
Descrição: dc.descriptionThe Human Genome and Stem Cell Research Center University of São Paulo-
Descrição: dc.descriptionUniversity of São Paulo Department of Pediatrics Medical School of Federal University of Minas Gerais-
Descrição: dc.descriptionPathology Department School of Medicine São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Neurology Medical School (FMUSP) University of São Paulo-
Descrição: dc.descriptionPathology Department School of Medicine São Paulo State University (UNESP)-
Idioma: dc.languageen-
Relação: dc.relationNeurology: Genetics-
???dc.source???: dc.sourceScopus-
Título: dc.titleManifesting carriers of X-linked myotubular myopathy: Genetic modifiers modulating the phenotype-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.