Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus.

ABSTRACT:

Purpose

Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster of chromosome 11p15.5 and often associated with loss of methylation (LOM) of the imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel the etiological mechanisms underlying these epimutations, we searched for genetic variants associated with IC2 LOM.

Methods

We looked for cases showing the clinical features of both BWS and long QT syndrome (LQTS), which is often associated with KCNQ1 variants. Pathogenic variants were identified by genomic analysis and targeted sequencing. Functional experiments were performed to link these pathogenic variants to the imprinting defect.

Results

We found three rare cases in which complete IC2 LOM is asso

SUBMITTER: Valente FM 

PROVIDER: S-EPMC6687501 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature