A 132 bp deletion affecting the KCNQ1OT1 gene associated with Silver-Russell syndrome clinical phenotype

Background Imprinting centre 2 (IC2) in the chromosomal region 11p15.5 regulates the monoallelic expression of imprinted genes by differential methylation of paternal and maternal chromosomes. Copy number variants in IC2 are associated with Beckwith-Wiedemann syndrome and Silver-Russell syndrome (SRS). Clinical outcome of IC2 deletions seems to depend on the parental origin of the chromosome, deletion size and inclusion or exclusion of enhancer and promoter regions. Results A paternally inherited 132 bp deletion within the KCNQ1OT1 gene was found in a proband with an SRS clinical phenotype. The patient's father and paternal grandmother, who both carry the deletion on their maternal chromosome, are unaffected. Review of other IC2 deletions and their associated clinical presentation was useful in understanding the genetic-phenotypic correlation. Conclusion Only six cases have been reported with deletions involving exclusively IC2, one being identical to our proband's 132 bp deletion. Our study, which is based on more extensive segregation data than the previous 132 bp deletion report, confirms the association of this deletion with growth restriction when paternally inherited. Remarkably, even though our patient has the same deletion, he has more pronounced phenotypic features; our findings thus suggest that some degree of clinical variability may be associated with this loss.