CDKN1C hyperexpression in two patients with severe growth failure and microdeletions affecting the paternally inherited KCNQ1OT1:TSS-DMR

CDKN1C is a negative regulator for cell proliferation. KCNQ1OT1:TSS-differentially methylated region (DMR) resides on chromosome 11p15.5 and regulates CDKN1C expression via KCNQ1OT1 expression. Paternal deletions involving the KCNQ1OT1:TSS-DMR result in variable phenotypes. However, expression analyses for CDKN1C in these patients are very limited. We identified two patients with prenatal and postnatal growth failure and clinical suspicion for Silver-Russell syndrome (SRS), having paternal microdeletions involving the KCNQ1OT1:TSS-DMR on 11p15.5, and demonstrated CDKN1C activation in both patients. Deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers, disrupt KCNQ1OT1 expression, strongly activate CDKN1C expression, and consequently caused severe growth failure in our patients. (By Dr. Masayo Kagami 鏡 雅代, https://jmg.bmj.com/content/early/2022/07/29/jmg-2022-108700 )

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