ICF syndrome: a new case and review of the literature

Abstract

Patients with ICF syndrome can be recognized by the presence of a variable immunodeficiency, instability of the pericentromeric heterochromatin of, in particular, chromosomes 1, 9, and 16 in cultured peripheral lymphocytes, and a number of facial anomalies. Recently, aberrations at the molecular level have been described, consisting of alterations in the methylation pattern of classical satellite DNA, in a number of patients. ICF syndrome is considered to be inherited in an autosomal recessive manner and may be rare, as only 14 patients have been described thus far. We present a new case, a boy with agammaglobulinemia, who was extensively studied by means of classical cytogenetics and fluorescent in situ hybridization. All patients previously reported in the literature are reviewed.

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

“…ICF syndrome patients also exhibit hypomethylation of satellite 2 repeats in the pericentromeric heterochromatin, and rearrangements of chromosomes 1, 9 and 16 via hypomethylated satellite 2 in lymphocytes to form multiradiate chromosomes (Jeanpierre et al, 1993;Xu et al, 1999). It should be noted that chromosomal rearrangements have been observed in bone marrow cells from only one of four patients studied (Fasth et al, 1990;Hulten, 1978;Smeets et al, 1994;Turleau et al, 1989), and have never been detected in fibroblast cells derived from four ICF syndrome patients (Brown et al, 1995;Carpenter et al, 1988;Maraschio et al, 1988;Tiepolo et al, 1979). Facial anomaly is another characteristic symptom afflicting individuals with ICF.…”

DNA methylation, methyltransferases, and cancer

“…A ected individuals demonstrate variable immunode®ciency consisting of an absence or severe reduction in at least two immunoglobulin isotypes and often su er from severe respiratory tract infections (Franceschini et al, 1995;Smeets et al, 1994). Developmental defects include a variable degree of mental impairment, delayed developmental milestones, and peculiar facial features such as low-set ears, hypertelorism,¯at nasal bridge, micrognathia, and macroglossia (Smeets et al, 1994).…”

DNA methylation in early development

“…Mutations in this protein are primarily point mutations resulting in partial loss of function (Hansen et al, 1999;Okano et al, 1999) while in mice complete loss of Dnmt3b in lethal (Okano et al, 1999). Children with ICF syndrome exhibit variable mental retardation, reduced growth, distinct facial abnormalities, and immunodeficiency leading to chronic infections severe enough to lead to death in many patients before adulthood (reviewed in Smeets et al, 1994;Ehrlich et al, 2008).…”