PMID- 19279649
OWN - NLM
STAT- MEDLINE
DCOM- 20090805
LR  - 20240312
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 10
IP  - 5
DP  - 2009 Jul
TI  - Molecular basis of complete complement C4 deficiency in two North-African 
      families with systemic lupus erythematosus.
PG  - 433-45
LID - 10.1038/gene.2009.10 [doi]
AB  - Complete deficiency of complement C4 is among the strongest genetic risk factors 
      for human systemic lupus erythematosus (SLE). C4 is a constituent of the 
      RP-C4-CYP21-TNX (RCCX) module in the human leukocyte antigen (HLA) that exhibits 
      inter-individual copy-number and gene-size variations. Here, we studied two 
      North-African families with complete C4 deficiency and SLE. The first included a 
      Moroccan male SLE patient (1P) and a sibling, who were both homozygous for 
      HLA-A*02 B*17 DRB1*07. The second had an Algerian female SLE patient (2P) 
      homozygous for HLA-A*01 B*17 DRB1*13. Early SLE disease onset, the presence of 
      photosensitive rashes, anti-Ro/SSA, renal disease and high titers of antinuclear 
      antibodies were the common features of complete C4 deficiency. Southern blot 
      analyses showed that 1P had monomodular RCCX with a long C4A, whereas 2P had 
      bimodular RCCX with one long C4A and one short C4B. Genomic DNA fragments for 
      these mutant genes were amplified and sequenced. A C>T transition that created 
      the R540X nonsense mutation in C4A was found in 1P. An identical 4-bp insertion 
      that generated the Y1537X nonsense mutation was discovered in both C4A and C4B of 
      2P. The high concordance of SLE and C4 deficiency among patients with non-DR3 and 
      non-DR2 haplotypes underscores the importance of C4 proteins in the protection 
      against SLE.
FAU - Wu, Y L
AU  - Wu YL
AD  - Center for Molecular and Human Genetics, The Research Institute at Nationwide 
      Children's Hospital, Columbus, OH 43205, USA.
FAU - Hauptmann, G
AU  - Hauptmann G
FAU - Viguier, M
AU  - Viguier M
FAU - Yu, C Y
AU  - Yu CY
LA  - eng
GR  - R01 AR050078/AR/NIAMS NIH HHS/United States
GR  - R01 AR054459-01A2/AR/NIAMS NIH HHS/United States
GR  - 1R01 AR050078/AR/NIAMS NIH HHS/United States
GR  - R01 AR054459/AR/NIAMS NIH HHS/United States
GR  - 1R01 AR054459/AR/NIAMS NIH HHS/United States
GR  - R01 AR050078-05/AR/NIAMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090312
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Complement C4)
RN  - 0 (HLA-A Antigens)
SB  - IM
MH  - Black People/genetics
MH  - Complement C4/*deficiency/genetics/immunology
MH  - Consanguinity
MH  - Female
MH  - HLA-A Antigens/genetics
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*genetics/*immunology
MH  - Male
MH  - Pedigree
PMC - PMC2767122
MID - NIHMS109413
EDAT- 2009/03/13 09:00
MHDA- 2009/08/06 09:00
PMCR- 2009/10/26
CRDT- 2009/03/13 09:00
PHST- 2009/03/13 09:00 [entrez]
PHST- 2009/03/13 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
PHST- 2009/10/26 00:00 [pmc-release]
AID - gene200910 [pii]
AID - 10.1038/gene.2009.10 [doi]
PST - ppublish
SO  - Genes Immun. 2009 Jul;10(5):433-45. doi: 10.1038/gene.2009.10. Epub 2009 Mar 12.