Identification of unique DNA methylation sites in Kabuki syndrome using whole genome bisulfite sequencing and targeted hybridization capture followed by enzymatic methylation sequencing

BackgroundKabuki syndrome (KS) is a congenital malformation syndrome caused by mutations in the KMT2D and KDM6A genes that encode histone modification enzymes. Although KS is considered a single gene disorder, its symptoms vary widely. Recently, disease-specific DNA methylation patterns, or episigna...

Full description

Saved in:
Bibliographic Details
Published in:Journal of human genetics 2022-12, Vol.67 (12), p.711-720
Main Authors: Hamaguchi, Yo, Mishima, Hiroyuki, Kawai, Tomoko, Saitoh, Shinji, Hata, Kenichiro, Kinoshita, Akira, Yoshiura, Koh-ichiro
Format: Article
Language:English
Subjects:
Bisulfite
Congenital defects
CpG islands
DNA fingerprinting
DNA methylation
Genomes
Histones
Hybridization
Pathogenesis
Peripheral blood
Phenotypes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BackgroundKabuki syndrome (KS) is a congenital malformation syndrome caused by mutations in the KMT2D and KDM6A genes that encode histone modification enzymes. Although KS is considered a single gene disorder, its symptoms vary widely. Recently, disease-specific DNA methylation patterns, or episignatures, have been recognized and used as a diagnostic tool for KS. Because of various crosstalk mechanisms between histone modifications and DNA methylation, DNA methylation analysis may have high potential for investigations into the pathogenesis of KS.ResultsIn this study, we investigated altered CpG-methylation sites that were specific to KS to find important genes associated with the various phenotypes or pathogenesis of KS. Whole genome bisulfite sequencing (WGBS) was performed to select target CpG islands, and enzymatic conversion technology was applied after hybridization capture to confirm KS-specific episignatures of 130 selected differently methylated target regions (DMTRs) in DNA samples from the 65 participants, 31 patients with KS and 34 unaffected individuals, in this study. We identified 26 candidate genes in 22 DMTRs that may be associated with KS. Our results indicate that disease-specific methylation sites can be identified from a small number of WGBS samples, and hybridization capture followed by enzymatic methylation sequencing can simultaneously test the sites.ConclusionsAlthough DNA methylation can be tissue-specific, our results suggest that methylation profiling of DNA extracted from peripheral blood may be a powerful approach to study the pathogenesis of diseases.
ISSN:1434-5161
1435-232X
DOI:10.1038/s10038-022-01083-4