The human homologue (PEG3) of the mouse paternally expressed gene 3 (Peg3) is maternally imprinted but not mutated in women with familial recurrent hydatidiform molar pregnancies.
OBJECTIVE
We mapped a locus for autosomal recessive molar pregnancies with biparental genomic contribution to chromosome 19q13.4 between D19S924 and D19S890. This 5-Mb region is homologous to proximal mouse chromosome 7 and contains a cluster of Krüppel-type zinc finger genes, including the human homologue of the mouse imprinted genes: the paternally expressed gene 3 (PEG3) and the maternally expressed Zim1 genes. We analyzed the PEG3 gene for mutations in women with familial recurrent hydatidiform moles and to determine its imprinting status in humans.


METHODS
We used database searches and screened cDNA libraries to find the complete genomic structure of PEG3. Polymerase chain reaction (PCR) amplification and direct sequencing of coding exons and flanking introns were performed on genomic DNA from the affected women. Allele-specific methylation and expression were studied by methylation-sensitive Southern analysis of a 5' located CpG island and by reverse-transcription PCR of total lymphoblast-derived RNA of normal individuals who were informative for two expressed polymorphisms.


RESULTS
We did not detect any mutations in the coding region of PEG3 in the affected women. We observed allele-specific methylation of the CpG island and expression from the paternal allele in two independent informative pedigrees.


CONCLUSIONS
Consistent with the findings in the mouse, the human PEG3 gene is expressed from the paternal allele. Our data support that PEG3 is not mutated in women with familial recurrent hydatidiform moles, although mutations in the regulatory regions that might affect imprinting or transcriptional level of the gene could not be evaluated.
Van den Veyver
I B
IB
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. iveyver@bcm.tmc.edu
Norman
B
B
Tran
C Q
CQ
Bourjac
J
J
Slim
R
R
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D006828:Hydatidiform Mole / Q000737:chemistry / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D011247:Pregnancy; D011494:Protein Kinases; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; C097901:Peg3 protein, mouse; D011506:Proteins; D014157:Transcription Factors; D011494:Protein Kinases