No evidence of PEG1/MEST gene mutations in Silver-Russell syndrome patients.
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.
Kobayashi
S
S
Gene Research Center, Tokyo Institute of Technology, 4259 Nagatsuka-cho, Midori-ku, Yokohama 226-8501, Japan.
Uemura
H
H
Kohda
T
T
Nagai
T
T
Chinen
Y
Y
Naritomi
K
K
Kinoshita
E I
EI
Ohashi
H
H
Imaizumi
K
K
Tsukahara
M
M
Sugio
Y
Y
Tonoki
H
H
Kishino
T
T
Tanaka
T
T
Yamada
M
M
Tsutsumi
O
O
Niikawa
N
N
Kaneko-Ishino
T
T
Ishino
F
F
D024506:5' Flanking Region / Q000235:genetics; D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D017398:Alternative Splicing; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005091:Exons; D005796:Genes / Q000235:genetics; D006130:Growth Disorders / Q000473:pathology*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome
D011506:Proteins; C103637:mesoderm specific transcript protein; D004247:DNA