In a man with immunodeficiency and recurrent infections since childhood, associated with ficolin-3 deficiency (613860), Munthe-Fog et al. (2009) identified homozygosity for a 1-bp deletion (1637delC; rs28357092) in exon 5 of the FCN3 gene, resulting in a frameshift and premature termination. Other features included brain abscesses and recurrent warts on the fingers. He had normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine. Laboratory studies showed impaired complement deposition when acetylated bovine serum albumin was used, indicating a defect in complement activation. The patient was born of Macedonian and Albanian parents, each of whom was unaffected and heterozygous for the variant. The allele frequency of the variant was 0.01 among a total of 1,282 patients with various immunodeficiencies; all were heterozygous for the variant except the index patient.
Schlapbach et al. (2011) reported a premature infant with necrotizing enterocolitis who was homozygous for the c.1637delC polymorphism. He had severe FCN3 deficiency, and his parents, who were heterozygous for the polymorphism, had about 50% FCN3 levels compared to controls.
Michalski et al. (2012) reported a male infant born at 35 weeks' gestation who developed infection with Streptococcus agalactiae. Laboratory studies showed complete H-ficolin deficiency as well as low MBL, undetectable MASP2, and low L-ficolin (FCN2; 601624). He had no severe infections during a 5-year follow-up, but he did have microcephaly, poor growth, and mental retardation. The patient was homozygous for the common FCN3 truncating polymorphism.
Michalski et al. (2015) reported 2 unrelated patients with ficolin-3 deficiency due to homozygosity for the c.1637delC variant. One was a 50-year-old man with nephrotic syndrome due to membranous nephropathy. The other patient was an 11-month-old boy who had pneumonia before surgery to repair a cardiac ventricular septal defect. Michalski et al. (2015) concluded that the consequences of FCN3 deficiency are not clear-cut, and suggested that it may act as a disease modifier.
Michalski et al. (2012) evaluated serum H-ficolin levels in 613 neonates, and FCN3 genotypes in 529 neonates; all were of Polish descent. Genotype analysis revealed that 96% were homozygous wildtype, 3.8% were compound heterozygous, and 0.2% (1 infant) was homozygous for the variant allele. The protein was undetectable in the homozygous infant. Preterm delivery and low birthweight were significantly associated with low serum H-ficolin, but not with heterozygosity for the c.1637delC allele, even though the variant allele influenced the protein level. There was no association between heterozygosity for the allele and perinatal infections. Michalski et al. (2012) concluded that heterozygosity for the FCN3 variant does not seem to have major clinical importance.
