Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

Zhang,Ai-Qian; Liu,Yu-Xing; Jin,Jie-Yuan; Wang,Chen-Yu; Fan,Liang-Liang; Xu,Da-Bao

doi:10.3892/etm.2021.9941

Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

Authors:
- Ai-Qian Zhang
- Yu-Xing Liu
- Jie-Yuan Jin
- Chen-Yu Wang
- Liang-Liang Fan
- Da-Bao Xu
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: March 19, 2021 https://doi.org/10.3892/etm.2021.9941
Article Number: 510

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Deficiency of the sixth complement component (C6D) is a genetic disease associated with increased susceptibility to Neisseria meningitides infection. Individuals with C6D usually present with recurrent meningococcal disease (MD). According to the patients' C6 levels, C6D is divided into complete genetic deficiency of C6 and subtotal deficiency of C6 (C6SD). The present study reported on a Han Chinese pediatric patient with MD, in whom further investigation revealed a C6SD genetic lesion. A heterozygote nonsense mutation (c.1062C>G/p.Y354*) in the C6 gene was identified by Sanger sequencing. The mutation alters the tyrosine codon at position 354 to a termination codon and results in a truncated protein. In conclusion, the genetic lesion of a pediatric patient with C6SD who was diagnosed due to having MD was investigated and a novel pathogenic mutation in the C6 gene was identified. The study confirmed the clinical diagnosis for this patient with C6SD and also expanded the spectrum of C6 mutations.

View Figures

View References

1	DiScipio RG and Hugli TE: The molecular architecture of human complement component C6. J Biol Chem. 264:16197–16206. 1989.PubMed/NCBI
2	Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V and Roumenina LT: Complement system part II: Role in immunity. Front Immunol. 6(257)2015.PubMed/NCBI View Article : Google Scholar
3	Orren A, Owen EP, Henderson HE, van der Merwe L, Leisegang F, Stassen C and Potter PC: Complete deficiency of the sixth complement component (C6Q0), susceptibility to Neisseria meningitidis infections and analysis of the frequencies of C6Q0 gene defects in South Africans. Clin Exp Immunol. 167:459–471. 2012.PubMed/NCBI View Article : Google Scholar
4	Parham KL, Roberts A, Thomas A, Wurzner R, Henderson HE, Potter PC, Morgan BP and Orren A: Prevalence of mutations leading to complete C6 deficiency (C6Q0) in the Western Cape, South Africa and detection of novel mutations leading to C6Q0 in an Irish family. Mol Immunol. 44:2756–2760. 2007.PubMed/NCBI View Article : Google Scholar
5	Wurzner R, Orren A, Potter P, Morgan BP, Ponard D, Spath P, Brai M, Schulze M, Happe L and Gotze O: Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals. Clin Exp Immunol. 83:430–437. 1991.PubMed/NCBI View Article : Google Scholar
6	Ikinciogullari A, Tekin M, Dogu F, Reisli I, Tanir G, Yi Z, Garrison N, Brilliant MH and Babacan E: Meningococccal meningitis and complement component 6 deficiency associated with oculocutaneous albinism. Eur J Pediatr. 164:177–179. 2005.PubMed/NCBI View Article : Google Scholar
7	Xiang R, Fan LL, Huang H, Cao BB, Li XP, Peng DQ and Xia K: A novel mutation of GATA4 (K319E) is responsible for familial atrial septal defect and pulmonary valve stenosis. Gene. 534:320–323. 2014.PubMed/NCBI
8	Hobart MJ, Fernie BA, Fijen KA and Orren A: The molecular basis of C6 deficiency in the western Cape, South Africa. Hum Genet. 103:506–512. 1998.PubMed/NCBI View Article : Google Scholar
9	Orren A, Wurzner R, Potter PC, Fernie BA, Coetzee S, Morgan BP and Lachmann PJ: Properties of a low molecular weight complement component C6 found in human subjects with subtotal C6 deficiency. Immunology. 75:10–16. 1992.PubMed/NCBI
10	El Sissy C, Rosain J, Vieira-Martins P, Bordereau P, Gruber A, Devriese M, de Pontual L, Taha MK, Fieschi C, Picard C and Frémeaux-Bacchi V: Clinical and genetic spectrum of a large cohort with total and sub-total complement deficiencies. Front Immunol. 10(1936)2019.PubMed/NCBI View Article : Google Scholar
11	Wurzner R, Hobart MJ, Fernie BA, Mewar D, Potter PC, Orren A and Lachmann PJ: Molecular basis of subtotal complement C6 deficiency. A carboxy-terminally truncated but functionally active C6. J Clin Invest. 95:1877–1883. 1995.PubMed/NCBI View Article : Google Scholar
12	Rosenfield L, Cvetkovic A, Woodward K and Quirt J: Late presentation of subtotal C6 deficiency in a patient with recurrent Neisseria meningitides infections. Ann Allergy Asthma Immunol. 120:432–433. 2018.PubMed/NCBI View Article : Google Scholar
13	Westra D, Kurvers RA, van den Heuvel LP, Wurzner R, Hoppenreijs EP, van der Flier M, van de Kar NC and Warris A: Compound heterozygous mutations in the C6 gene of a child with recurrent infections. Mol Immunol. 58:201–205. 2014.PubMed/NCBI View Article : Google Scholar
14	Owen EP, Leisegang F, Whitelaw A, Simpson J, Baker S, Wurzner R, Potter P and Orren A: Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa. S Afr Med J. 102:525–527. 2012.PubMed/NCBI View Article : Google Scholar
15	Ram S, Lewis LA and Rice PA: Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev. 23:740–780. 2010.PubMed/NCBI View Article : Google Scholar
16	Nishizaka H, Horiuchi T, Zhu ZB, Fukumori Y, Nagasawa K, Hayashi K, Krumdieck R, Cobbs CG, Higuchi M, Yasunaga S, et al: Molecular bases for inherited human complement component C6 deficiency in two unrelated individuals. J Immunol. 156:2309–2315. 1996.PubMed/NCBI