| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p21.33 | ?Complement factor B deficiency | 615561 | Autosomal recessive | 3 | CFB | 138470 |
A number sign (#) is used with this entry because of evidence that complement factor B deficiency (CFBD) is caused by compound heterozygous mutation in the CFB gene (138470) on chromosome 6p21. One such family has been reported.
Slade et al. (2013) reported a 32-year-old woman, born of unrelated parents of English and Scottish heritage, who had a history of susceptibility to infection with encapsulated bacteria beginning in early childhood. She first presented at 2 years of age with pneumococcal peritonitis. Two years later, she had community-acquired pneumonia. At age 15 years, she developed Neisseria meningitis, and at age 30, she had pneumococcal pneumonia complicated by empyema and necessitating admission to the intensive care unit. Laboratory studies showed normal immunoglobulins and lymphocytes, but functional ELISA showed that the alternative complement pathway was inactive. The defect was not complemented by factor B-depleted serum, and factor B was undetectable by radial immunodiffusion. The patient was treated with vaccination and prophylactic antibiotics without recurrence.
The transmission pattern of complement factor B deficiency in the family reported by Slade et al. (2013) was consistent with autosomal recessive inheritance.
In a woman with complement factor B deficiency, Slade et al. (2013) identified compound heterozygous truncating mutations in the CFB gene (138470.0007 and 138470.0008). The mutations were found by genome sequencing of the CFB gene and segregated with the disorder in the family. Complement studies in the parents showed normal activity of the alternative complement pathway. The findings illustrated the role of complement factor B in the protection against infection with encapsulated organisms.
Hauptmann et al. (1980) stated that 11 allotypes of Bf are known and that the principal, perhaps only, site of synthesis is the liver inasmuch as the recipient of a liver graft lost his own Bf type and acquired the donor's type. Furthermore, they observed deficiency of properdin factor B transmitted through 3 generations of a family in association with haplotype HLA-A11, B27. The deficiency had no apparent consequences in heterozygotes.
Hauptmann, G., Tongio, M. M., Klein, J., Mayer, S., Cinqualbre, J., Jeanblanc, B., Kieny, R., Mauff, G., Federmann, G. Le facteur B de la properdine: polymorphism, lieu de synthese et premier cas de deficit genetique. Nouv. Presse Med. 9: 45 only, 1980. [PubMed: 6898304]
Slade, C., Bosco, J., Unglik, G., Bleasel, K., Nagel, M., Winship, I. Deficiency in complement factor B. (Letter) New Eng. J. Med. 369: 1667-1669, 2013. [PubMed: 24152280] [Full Text: https://doi.org/10.1056/NEJMc1306326]