ZBTB24 is a transcriptional regulator which was first reported in relation to autosomal recessive immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome 2 in 2011 (de Greef et al., PMID: 21596365). ICF syndrome 2 is characterized by facial dysmorphism, agammaglobulinemia, recurrent infections, intellectual disability, chromosome instability, and T-cell functional deficiency. Heterozygous carriers are clinically unaffected. Nine variants (missense, nonsense, and frameshift) that have been reported in eight probands in three publications (PMIDs: 21596365, 32061411, 23486536) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by mouse models, expression studies, and in vitro functional assays (PMIDs: 39562305, 32865561, 27626380, 21596365). In summary, there is definitive evidence supporting the relationship between ZBTB24 and autosomal recessive immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome 2. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.This classification was approved by the ClinGen SCID-CID GCEP on the meeting date July 17, 2025 (SOP Version 11)].
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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