Maternal versus paternal inheritance of a 132 bp 11p15.5 microdeletion affecting KCNQ1OT1 and associated phenotypes

In this brief communication, we address the possible associations of a 132 bp deletion within the antisense gene KCNQ1OT1 on 11p15.5 to growth abnormalities. We question its recently suggested connection of paternal inheritance with Silver-Russell syndrome (SRS; OMIM #180860) and demonstrate maternal inheritance of the same variant in a 16-year-old girl with a tumour of the left leg. She also had mild isolated hemihypertrophy, suggesting a possible link to Beckwith-Wiedemann syndrome (BWS; OMIM #130650). Our findings underscore the complexity of 11p15.5 structural variations and the diffidence required when assessing their pathogenicity. Genetic alterations of 11p15.5 imprinted gene clusters (regulated by imprinting centres H19/IGF2:IG-DMR (IC1) and KCNQ1OT1:TSS-DMR (IC2)) contribute to the phenotypically inverse growth disorders Beckwith-Wiedemann syndrome (BWS; OMIM #130650) and Silver-Russell syndrome (SRS; OMIM #180860).1 2 BWS shows locus heterogeneity within the 11p15.5 chromosomal region, where IC2 loss of methylation, IC1 gain of methylation, 11p15.5 UPD/CNV...
Source: Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Open access Epigenetics Source Type: research