No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients

Silver-Russell syndrome (SRS) is characterized by prenatal and postnatal gr owth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on c hromosome 7q32 that is expressed only from the paternal allele and is a, ca ndidate gene for SRS. To clarify its biological function and role in SRS, w e screened PEG1/MEST abnormalities in 15 SRS patients from various standpoi nts. 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 detec t any mutations in the PEG1/MEST a coding region, and there were no signifi cant 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 a were normally mainta ined 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. (C) 2001 Wiley-Liss, Inc.