NBDC Research ID: hum0368.v1



Aims: ICF (immunodeficiency, centromeric instability, facial anomaly) syndrome is a rare congenital autosomal recessive genetic disorder characterized by immunodeficiency, chromosomal instability with DNA hypomethylation, and facial anomalies. Previous studies have revealed that ICF patients can be divided into four subtypes according to their causative genes (DNMT3B, ZBTB24, CDCA7, or HELLS). However, there are still a few patients whose causative genes are unknown. In this study, we identified UHRF1 as a novel causative gene in one such patient and performed whole-genome bisulfite sequencing analysis of DNA extracted from peripheral blood cells of this patient to identify a DNA hypomethylation pattern characteristic of this patient.

Methods: DNA was extracted from peripheral blood cells, and prepared libraries by the post-bisulfite adaptor-tagging (PBAT) method. Then whole genome sequencing was performed and determined the methylation status of all cytosines.

Participants/Materials: ICF syndrome


Dataset IDType of DataCriteriaRelease Date
JGAS000559 NGS (PBAT-seq) Controlled-access (Type I) 2022/11/29

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Participants/Materials ICF syndrome (ICD10: D800) : 1 case
Targets PBAT-seq
Target Loci for Capture Methods -
Platform Illumina [NovaSeq 6000]
Library Source DNAs extracted from peripheral blood cells (Amplification-free)
Cell Lines -
Library Construction (kit name) Post-Bisulfite Adaptor-Tagging (PBAT)*1
Fragmentation Methods Bisulfite Treatment
Spot Type Single-end
Read Length (without Barcodes, Adaptors, Primers, and Linkers) 100 bp
Japanese Genotype-phenotype Archive Dataset ID JGAD000681
Total Data Volume 46.4 GB (fastq)
Comments (Policies) NBDC policy

*1Miura et al., Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor tagging. Nucleic Acids Res., 40, e136, 2012



Principal Investigator: Motoko Unoki

Affiliation: Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University

Project / Group Name: -

Funds / Grants (Research Project Number):

NameTitleProject Number
KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area) Mechanisms underlying maintenance of genome integrity by DNA methylation 19H05740
KAKENHI Grant-in-Aid for Scientific Research (C) Molecular pathogenesis of ICF syndrome 18K06961
KAKENHI Grant-in-Aid for Scientific Research (A) ICF syndrome and the molecular network regulating the human epigenome 26253020
Yamada Science Foundation Novel DNA methylation maintenance mechanism for centromeric and pericentromeric repeats -



TitleDOIDataset ID
1 Novel compound heterozygous mutations in UHRF1 are associated with atypical immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome with distinctive genome-wide DNA hypomethylation. doi: 10.1093/hmg/ddac291 JGAD000681


USRES (Controlled-access Data)

Principal InvestigatorAffiliationCountry/RegionResearch TitleData in Use (Dataset ID)Period of Data Use