Absence of an obvious molecular imprinting mechanism in a human fetus with monoallelic IGF2R expression.

We have previously shown that, in contrast to its murine homologue, the human IGF2R gene is not imprinted. However, in a small number of individuals, partial or complete repression of the paternal allele has been observed and it has been speculated that in man, IGF2R imprinting is a polymorphic trait. We have confirmed monoallelic IGF2R expression in one fetus and investigated whether genomic imprinting was involved in the silencing of the paternal allele. Two CpG rich regions, known to be important for the imprinted expression of Igf2r in mice, were examined for sequence and methylation changes. A 17 bp deletion was identified within the intronic CpG island. This deletion was shown to be polymorphic and without consequence for the expression of the relevant IGF2R allele. Furthermore, in this fetus, methylation patterns of the intronic and promoter CpG islands were identical to that of normal controls, including hypomethylation of the paternal promoter region. In mice, this region is hypermethylated on the paternal allele which is silenced. The absence of paternal promoter methylation indicates that paternal silencing in this particular fetus is by a mechanism other than parental imprinting or, alternatively, that promoter methylation is not necessary for IGF2R imprinting. Copyright 1998 Academic Press.