title: Total C4B deficiency due to gene deletion and gene conversion in a patient with severe infections.
abstract: Deficiencies of the early components of the classical complement pathway impair the actions of innate and humoral immunity and may lead to increased susceptibility to infections. We have studied the genetic basis of total C4B deficiency in a Finnish patient with recurrent meningitis, chronic fistulas and abscesses. The maternal chromosome carried a four-gene deletion including the C4B gene, and a conversion from C4B to C4A gene was found on the paternal chromosome resulting in complete deficiency of C4B. In the converted C4A gene, mutation screening did not reveal any amino acid changes or prominent mutations, yet a large number of nucleotide variations were found. Further, the patient was heterozygous for structural deficiency of mannan binding lectin (MBL) associating with medium levels of serum MBL. Our data provides new information on the genetic instability of the C4 gene region, and on the association of homozygous C4B deficiency and variant MBL genotype with increased susceptibility to recurrent and chronic infections. Importantly, plasma therapy induced a prompt clinical cure with long-term effects.
authors.affiliation: Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Jaatinen
authors.forename: Meri
authors.initials: M
authors.lastname: Lahti
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: Riikka
authors.initials: R
authors.lastname: Kinos
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
mesh_terms: D000293:Adolescent; D015139:Blotting, Southern; D015935:Complement C4b / Q000235:genetics*; D003171:Complement Pathway, Classical / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005785:Gene Conversion; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D007239:Infections / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D012720:Severity of Illness Index
chemical_list: D015935:Complement C4b