Table 1.

Summary of the non-concordant clinical and molecular features between ICF1 and ICF2–4 patients

ICF1ICF2–4
Immunodeficiency More pronounced and earlier diagnosis Less extreme Ig class deficiencies 
Intellectual disability Lower prevalence Higher prevalence 
Gender bias No significant bias noted Majority male 
Satellite DNA hypomethylation Satellite II and III (common to all ICF) subtelomeric hypomethylation Satellite II and III; α-satellite hypomethylation 
Telomere biology Elevated TERRA expression and telomere shortening Not reported 
Germline gene promoter methylation Hypomethylation and upregulation of MAEL and SYCE1 Not reported 
Genome-wide DNA methylation Hypomethylation of promoters of germline genes Hypomethylation of CpG-poor heterochromatin 
CSR Unexplored Low IgG and IgA 
ICF1ICF2–4
Immunodeficiency More pronounced and earlier diagnosis Less extreme Ig class deficiencies 
Intellectual disability Lower prevalence Higher prevalence 
Gender bias No significant bias noted Majority male 
Satellite DNA hypomethylation Satellite II and III (common to all ICF) subtelomeric hypomethylation Satellite II and III; α-satellite hypomethylation 
Telomere biology Elevated TERRA expression and telomere shortening Not reported 
Germline gene promoter methylation Hypomethylation and upregulation of MAEL and SYCE1 Not reported 
Genome-wide DNA methylation Hypomethylation of promoters of germline genes Hypomethylation of CpG-poor heterochromatin 
CSR Unexplored Low IgG and IgA 

TERRA, telomeric repeat-containing RNA.

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