C5 complement deficiency in a Saudi family, molecular characterization of mutation and literature review.
BACKGROUND
Complement deficiencies are rare primary immunodeficiency disorders, the diagnosis of which is often underestimated. Only a small number of molecular studies have been carried out for the characterization of the underlying genetic defects in these cases.


OBJECTIVE
Reporting the first family from the Arabian Gulf region with multiple members affected by meningococcemia and abscent serum complement 5 (C5). We tried to correlate clinical, biochemical and molecular genetics features of this family.


METHODS
Determination of the serum level of all complement proteins including the terminal cascade (C5-9), followed by mutation analysis on DNA extracted from fresh blood samples of each alive family member.


RESULTS
Molecular studies showed a homozygous nonsense mutation in exon 1, with the change of cytosine to thymine at position 55 (55C > T) leading to change of the glutamine amino acid at position 19 to a stop codon (Q19X), and serologically absence of C5 in the serum. A similar but compound heterozygous mutation has been reported in one African-American family. previously.


CONCLUSIONS
Characterization of the underlying mutations in C5 deficient families is important, to understand this uncommon complement deficiency, and try to elucidate structure-function relationships in the C5 gene. This report also highlights the importance of complement screening in cases of sporadic meningococcal Infections, especially in communities with high prevalence of consanguineous marriages, which will ensure timely and adequate clinical interventions.
King Faisal specialist Hospital & Research Center, PO Box 3354, MBC 46, Riyadh, 11211, Kingdom of Saudi Arabia. rarnaout@kfshrc.edu.sa
Rand
R
Arnaout
Sahar
S
Al Shorbaghi
Hasan
H
Al Dhekri
Hamoud
H
Al-Mousa
Abdulaziz
A
Al Ghonaium
Bandar
B
Al Saud
Saleh
S
Al Muhsen
Lina
L
Al Baik
Abbas
A
Hawwari
D002675:Child, Preschool; D003182:Complement C5 / Q000172:deficiency* / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008589:Meningococcal Infections / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D010375:Pedigree; D012529:Saudi Arabia; D017384:Sequence Deletion / Q000235:genetics; D013329:Structure-Activity Relationship
D003182:Complement C5