Vesicourethral reflux‐induced renal failure in a patient with ICF syndrome due to a novel DNMT3B mutation

Abstract

ICF syndrome is a primary immunodeficiency disease characterized by hypo- or agammaglobulinemia, centromeric instability mainly on chromosomes 1, 9, and 16 and facial anomalies. ICF syndrome presents with frequent respiratory tract infections in infancy. A 20-month-old female patient was referred to our clinic due to frequent lower respiratory tract infections. ICF syndrome was considered because of comorbidity of hypogammaglobulinemia, facial anomalies, and neuromotor growth retardation. Metaphase chromosome analysis revealed centromeric instability on chromosomes 1, 9, and 16 and through Sanger a previously unreported homozygous missense mutation (c.1805T>C; [p.V602A]) was identified in the DNMT3B, confirming ICF1. The patient was found to have a breakdown in renal function 1 year later; the urinary system was examined and bilateral vesicoureteral reflux was found, warranting the need for dialysis in time. This report expands the mutation spectrum of ICF1 and is the first to describe bilateral vesicoureteral reflux accompanying ICF syndrome. © 2016 Wiley Periodicals, Inc.

Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2

“…With these new cases included, the total number of genetically confirmed ICF cases reported to date is 77 (including patient 2 from Franceschini et al 16 with ZBTB24 mutations [unpublished F. Licciardi]), of which 56% have mutations in DNMT3B, 31% have mutations in ZBTB24, and the remaining 13% have mutations in CDCA7 or HELLS. This study, combined with earlier mutation reports, 1,2,4,11,12,15,[17][18][19][20][21] also revealed a gender bias specific to the ICF2 population with 79% of all ICF2 patients being male. In summary, we expand the mutation spectrum for the 2 most common genetic causes of ICF, show that complete absence of the ZBTB24 locus is compatible with human life, and identify a gender bias in ICF2.…”

“…With the identification of mutations in 12 ICF syndrome cases, a total of 77 genetically confirmed ICF patients have been reported. 1,2,4,11,12,15,[17][18][19][20][21] Fifty-six percent of the ICF syndrome patients carry mutations in DNMT3B, 31% carry mutations in ZBTB24, 6.5% carry mutations in CDCA7, and 6.5% carry mutations in HELLS ( Figure 3A). We observed a gender bias in the ICF2 population, with 19 male patients and only 5 female patients out of 24 patients reported ( Figure 3B).…”