Tissue-Specific Size and Methylation Analysis in Two Fragile X Families: Contribution to the Clinical PhenotypeEdith RQM1, Silvia J2, Inmaculada R3, Alicia G3, Raquel M1, Pablo M2 and Elizabeth P1,4*
2Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Vírgen del Rocío/ CSIC/ Universidad de Sevilla, Seville, Spain
- *Corresponding Author:
- Elizabeth Pintado
Departamento de Bioquímica y
Biología Molecular e Inmunología
Facultad de Medicina, Avda Sánchez Pizjuán
4 Universidad de Sevilla, 41009, Sevilla, Spain
E-mail: [email protected]
Received date: June 29, 2016; Accepted date: October 05, 2016; Published date: October 10, 2016
Citation: Edith RQM, Silvia J, Inmaculada R, Alicia G, Raquel M, et al. (2016) Tissue-Specific Size and Methylation Analysis in Two Fragile X Families: Contribution to the Clinical Phenotype. J Mol Genet Med 10:227 doi:10.4172/1747-0862.1000227
Copyright: © 2016 Edith RQM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Methylation at critical CpG sites on the expanded FMR1 gene is crucial for pathological manifestation of fragile X syndrome and fragile X-related disorders. Methylation status from blood, oral mucosa and root hair was analyzed with the FMR1 mPCR kit (Asuragen). Differential allele expression was studied by TP-PCR. Psychological and neurological explorations were performed in the probands. Patient II-1 of family 1 showed an extremely skewed X-chromosome inactivation of the normal allele in blood, oral mucosa cells and root hair. Analysis of differential expression of both alleles in blood showed the preferential expression of the expanded allele. Similarly, patient II-3 of family 2 showed an extremely skewed X-chromosome inactivation of the normal allele in blood, oral mucosa and root hair. Both females presented clinical features compatible with their skewed methylation toward the normal allele. Methylation analysis at critical CpG sites in the first FMR1 exon may predict clinical manifestations in carriers of premutation or full mutation. Analysis of differential expression of both alleles in women using TP-PCR could contribute to clarify the real impact of skewed methylation on the phenotype.