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Total C4B deficiency due to gene deletion and gene conversion in a patient with severe infections

Jaatinen, Taina; Lahti, Meri; Ruuskanen, Olli; Kinos, Riikka; Truedsson, Lennart LU ; Lahesmaa, Riitta and Lokki, Marja-Liisa (2003) In Clinical and Diagnostic Laboratory Immunology 10(2). p.195-201
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Diagnostic Laboratory Immunology
volume
10
issue
2
pages
195 - 201
publisher
American Society for Microbiology
external identifiers
  • wos:000181566700001
  • pmid:12626442
  • scopus:0037338611
ISSN
1071-412X
DOI
10.1128/CDLI.10.2.195-201.2003
language
English
LU publication?
yes
id
eefc5c2e-85b1-44c1-b6db-a7fb1b4b6ee4 (old id 141815)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12626442&query_hl=33
date added to LUP
2007-07-25 13:55:21
date last changed
2018-05-29 11:46:01
@article{eefc5c2e-85b1-44c1-b6db-a7fb1b4b6ee4,
  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.},
  author       = {Jaatinen, Taina and Lahti, Meri and Ruuskanen, Olli and Kinos, Riikka and Truedsson, Lennart and Lahesmaa, Riitta and Lokki, Marja-Liisa},
  issn         = {1071-412X},
  language     = {eng},
  number       = {2},
  pages        = {195--201},
  publisher    = {American Society for Microbiology},
  series       = {Clinical and Diagnostic Laboratory Immunology},
  title        = {Total C4B deficiency due to gene deletion and gene conversion in a patient with severe infections},
  url          = {http://dx.doi.org/10.1128/CDLI.10.2.195-201.2003},
  volume       = {10},
  year         = {2003},
}