Phenotypic Diversity of Chronic Granulomatous Disease within a Family carrying the Same NCF1 Gene Mutation
-
Sarvin Yazdizadeh
,
Mohammad Saberi
,
Abdollah Karimi
,
Samin Sharafian
,
Sedigheh Rafiei Tabatabaei
,
Sahar Seraj
,
Maryam Sadat Seyedmehdi
,
Shahrzad Fallah
Abstract
Chronic Granulomatous Disease (CGD) is a defect or abnormality in the immune system that produces severe and persistent signs and symptoms in affected individuals.
There are phenotypic diversity and genetic heterogeneity among patients with inborn errors of immunity (IEI). Symptoms may vary even when the mutations are identical; conversely, patients with different mutations may have similar clinical features. The expression of phenotype may be determined by the gene sequence, epigenetic changes, and sometimes environmental factors. Some of these outcomes are influenced by the individual’s past immunological exposure.
This study discusses two CGD cases, a father and son; after the diagnosis of CGD in the child and confirmation of the genetic mutation, the same mutation was also identified in the father.
Therefore, physicians should have more awareness that a single genetic mutation can have different clinical manifestations.
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16. Tajik S, Badalzadeh M, Fazlollahi MR, Houshmand M, Bazargan N, Movahedi M, et al. Genetic and molecular findings of 38 Iranian patients with chronic granulomatous disease caused by p47-phox defect. Scand J Immunol. 2019;90(1):e12770.
17. Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Wolach O, Grisaru-Soen G, et al. Analysis of chronic granulomatous disease in the Kavkazi population in Israel reveals phenotypic heterogeneity in patients with the same NCF1 mutation. J Clin Immunol. 2018;38(2):193-203.
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24. Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, et al. Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease. J Allergy Clin Immunol.
2023;152(6):1619-33.
2. Song EK, Jaishankar GB, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10.
3. Heyworth PG, Cross AR, Curnutte JT. Chronic granulomatous disease. Curr Opin Immunol.
2003;15(3):578-84.
4. Casimir CM, Bu-Ghanim HN, Rodaway ARF, Bentleyt DL, Rowe P, Segal AW. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat. Proc Natl Acad Sci U S A. 1991;88(5):11172-6.
5. Brunson T, Wang Q, Chambers I, Song Q. A copy number variation in human NCF1 and its pseudogenes. BMC Genet. 2010;11(1):13.
6. Sacco KA, Gazzin A, Notarangelo LD, Delmonte OM. Granulomatous inflammation in inborn errors of immunity. Front Pediatr. 2023;11(3):105.
7. Li T, Zhou X, Ling Y, Jiang N, Ai J, Wu J, et al. Genetic and clinical profiles of disseminated bacillus CalmetteGuérin disease and chronic granulomatous disease in China. Front Immunol. 2019;10(1):13.
8. Cotter DJ, Severson AL, Kang JTL, Godrej HN, Carmi S, Rosenberg NA. Modeling the effects of consanguinity on autosomal and X-chromosomal runs of homozygosity and identity-by-descent sharing. G3 (Bethesda).
2024;14(2):jkad112.
9. Bittles AH. Consanguinity and its relevance to clinical genetics. Clin Genet. 2001;60(1):89-98.
10. Cooper DN, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H. Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum Genet. 2013;132:1077-130.
11. Nepesov S, Firtina S, Aygun FD, Burtenece N, Cokugras H, Camcioglu Y. Diagnosis of primary immunodeficiency diseases in pediatric patients hospitalized for recurrent, severe, or unusual infections. Allergol Immunopathol (Madr). 2022;50(4):50-6.
12. Fattahi F, Badalzadeh M, Sedighipour L, Movahedi M, Fazlollahi MR, Mansouri SD, et al. Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease. J Clin Immunol. 2011;31(5):792801.
13. Mortaz E, Azempour E, Mansouri D, Tabarsi P, Ghazi M, Koenderman L, et al. Common infections and target organs associated with chronic granulomatous disease in Iran. Int Arch Allergy Immunol. 2019;179:62-73.
14. O’Donovan CJ, Tan LT, Abidin MAZ, Roderick MR, Grammatikos A, Bernatoniene J. Diagnosis of chronic granulomatous disease: strengths and challenges in the genomic era. J Clin Med. 2024;13:165.
15. Rawat A, Vignesh P, Sudhakar M, Sharma M, Suri D, Jindal A, et al. Clinical, immunological, and molecular profile of chronic granulomatous disease: a multi-centric study of 236 patients from India. Front Immunol. 2021;12:667.
16. Tajik S, Badalzadeh M, Fazlollahi MR, Houshmand M, Bazargan N, Movahedi M, et al. Genetic and molecular findings of 38 Iranian patients with chronic granulomatous disease caused by p47-phox defect. Scand J Immunol. 2019;90(1):e12770.
17. Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Wolach O, Grisaru-Soen G, et al. Analysis of chronic granulomatous disease in the Kavkazi population in Israel reveals phenotypic heterogeneity in patients with the same NCF1 mutation. J Clin Immunol. 2018;38(2):193-203.
18. Kammenga JE. The background puzzle: how identical mutations in the same gene lead to different disease symptoms. FEBS J. 2017;284:3362-73.
19. Maglione PJ, Simchoni N, Cunningham-Rundles C. Toll- like receptor signaling in primary immune deficiencies.
Ann N Y Acad Sci. 2015;1356:1-21.
20. Li S, Liu J, Zhang X, Gu Q, Wu Y, Tao X, et al. The potential impact of antibiotic exposure on the microbiome and human health. Microorganisms. 2025;13:456.
21. Kaur G, Singh S, Nanda S, Zafar MA, Malik JA, Arshi MU, et al. Fiction and facts about BCG imparting trained immunity against COVID-19. Vaccines (Basel).
2022;10:234.
22. Rook GAW, Bloomfield SF. Microbial exposures that establish immunoregulation are compatible with targeted hygiene. J Allergy Clin Immunol. 2021;148(1):33-9.
23. Reynolds HM, Bettini ML. Early-life microbiota-immune homeostasis. Front Immunol. 2023;14(5):678.
24. Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, et al. Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease. J Allergy Clin Immunol.
2023;152(6):1619-33.
| Files | ||
| Issue | Articles in Press | |
| Section | Case Report(s) | |
| Keywords | ||
| Chronic granulomatous disease Consanguinity Mutation Neutrophil cytosolic factor 1 Phenotype | ||
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How to Cite
1.
Yazdizadeh S, Saberi M, Karimi A, Sharafian S, Rafiei Tabatabaei S, Seraj S, Sadat Seyedmehdi M, Fallah S. Phenotypic Diversity of Chronic Granulomatous Disease within a Family carrying the Same NCF1 Gene Mutation. Iran J Allergy Asthma Immunol. 2025;:1-7.
