X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients
Por:
Xiol-Viñas C, Vidal-Falcó S, Pascual-Alonso A, Blasco-Perez L, Brandi-Tarrau N, Pacheco-Fernández P, Gerotina E, O'Callaghan-Gordo M, Pineda M and Armstrong-Moron J
Publicada:
19 ago 2019
Ahead of Print:
19 ago 2019
Categoría:
Multidisciplinary
Resumen:
Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern.
Filiaciones:
Xiol-Viñas C:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Vidal-Falcó S:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Pascual-Alonso A:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Blasco-Perez L:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Brandi-Tarrau N:
Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
Pacheco-Fernández P:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Gerotina E:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
O'Callaghan-Gordo M:
Neurology Service, Hospital Sant Joan de Deu, Barcelona, Spain
Pineda M:
Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain
Armstrong-Moron J:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain.
Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain.
CIBER-ER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain.
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