Asunto(s)
Anomalías Múltiples/genética , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Mutación/genética , Factores de Transcripción/genética , ADN/química , ADN/genética , Enzimas Reparadoras del ADN , Femenino , Dosificación de Gen , Humanos , Hidrolasas , Japón , Masculino , Glicoproteínas de Membrana , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , SíndromeAsunto(s)
Anomalías Múltiples/genética , Proteínas Portadoras/genética , Trastornos del Crecimiento/patología , Discapacidad Intelectual/patología , Péptidos y Proteínas de Señalización Intracelular , Proteínas Nucleares/genética , Anomalías Múltiples/patología , Adolescente , Adulto , Niño , Preescolar , ADN/química , ADN/genética , Análisis Mutacional de ADN , Femenino , Eliminación de Gen , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina , Humanos , Masculino , Mutación , SíndromeRESUMEN
Silver-Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (alpha and beta) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST alpha coding region, and there were no significant mutations in the 5'-flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST alpha were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS.