Transcript 2B of RB1 is imprinted and paternally expressed whereas the main RB1 transcript shows
preferential maternal expression (Kanber
D et al, 2009). A DMR (PPP1R26P1) within a 1.2 kb CpG island (CpG 85) within intron 2 of RB1 is
from a retrotransposition of part of exon 3 and exon 4 of PPP1R26 (KIAA0649). In 5 individuals this
CpG island was methylated on the maternal allele and unmethylated on the paternal allele. CpG 85
contains a novel start exon (2B). Limited evidence suggests paternal expression of the
2B-transcript which is postulated to interfere with the paternal full length RB1 transcript.
Maternal methylation of CpG 85 has been confirmed by Nakabayashi K et al (2011) and Eloy P et al (2016).
Prickett AR et al (2015) reported
hypermethylation of a CpG island (1 kb from the reported DMR) in 13/18 patients with Silver Russell
Previous evidence suggested parent-of-origin effects on the transmission of retinoblastoma
susceptibility in humans (Naumova
A et al, 1994), and in mice (earlier onset of tumours when mutant Rb is paternally inherited)
AY et al, 1997). This parent of origin effect may be more prominent for hypomorphic alleles (Eloy P et al, 2016; Imperatore V et al, 2018).
In isolated unilateral retinoblastoma, tumours having loss of the maternally derived RB1 allele had an
earlier age of onset than those having paternal loss (Schuler A et al, 2005).
In an unexplained observation, the parental origin of a chromosomal rearrangement near RB affected
the NruI restriction enzyme
digestion pattern (Blanquet V et al, 1991).
De novo mutations of RB preferentially occur during male gametogenesis - this is not usually
regarded as an imprinting effect (see parental origin of de novo mutations section of this database).