Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease

A cohort study from Oman

Arwa Al Riyami, S. Al-Zadjali, S. Al-Mamari, B. Al-Said, J. Al-Qassabi, Salem Al-Tamemi

Research output: Contribution to journalArticle

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Abstract

Background: Chronic granulomatous disease (CGD) is an X-linked (XL) or autosomal recessive (AR) primary immunodeficiency disease. Respiratory burst assessment by flow cytometry is a rapid test of granulocyte stimulation, and results predict the underlying genotype. This study aims to describe the immune-phenotypic profile of patients with CGD diagnosed in our center and correlate that with underlying genetic mutations. Methods: Immuno-phenotypic and genetic data on all patients with CGD diagnosed at Sultan Qaboos University Hospital (SQUH) were reviewed. Results: A total of 32 patients were diagnosed with CGD using molecular studies. Genetically confirmed individuals included 1 patient with XL-CGD (a large deletion involving the CYBB and XK genes resulting in a McLeod phenotype), 27 patients with AR-CGD with a c.579G>A (p.Trp193X) mutation at the NCF1 gene, and 4 patients with AR-CGD with a c.784G>A (p.Gly262Ser) mutation at the NCF1 gene. Flow cytometry and molecular results were available for comparison in 26 patients with AR-CGD. The patients with AR-CGD had a range of flow cytometry-generated fluorescent patterns as follows: reduced neutrophil stimulation with a sharp peak (12/26), reduced neutrophil stimulation with a broad peak (11/26), and a complete lack of neutrophil stimulation (3/26). No consistent flow cytometry-generated fluorescent pattern was observed in either of the 2 AR mutations identified in our patients. Conclusion: Flow cytometry is a robust test of CGD diagnosis. However, results should be interpreted with caution when predicting the underlying probable genotype, and results need to be complemented with definitive molecular studies.

Original languageEnglish
Pages (from-to)592-596
Number of pages5
JournalInternational Journal of Laboratory Hematology
Volume40
Issue number5
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Oman
Chronic Granulomatous Disease
Flow cytometry
Flow Cytometry
Cohort Studies
Mutation
Neutrophils
Genes
Genotype
Respiratory Burst
Granulocytes

Keywords

  • flow cytometry
  • immune deficiency
  • molecular genetics

ASJC Scopus subject areas

  • Hematology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease : A cohort study from Oman. / Al Riyami, Arwa; Al-Zadjali, S.; Al-Mamari, S.; Al-Said, B.; Al-Qassabi, J.; Al-Tamemi, Salem.

In: International Journal of Laboratory Hematology, Vol. 40, No. 5, 01.10.2018, p. 592-596.

Research output: Contribution to journalArticle

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abstract = "Background: Chronic granulomatous disease (CGD) is an X-linked (XL) or autosomal recessive (AR) primary immunodeficiency disease. Respiratory burst assessment by flow cytometry is a rapid test of granulocyte stimulation, and results predict the underlying genotype. This study aims to describe the immune-phenotypic profile of patients with CGD diagnosed in our center and correlate that with underlying genetic mutations. Methods: Immuno-phenotypic and genetic data on all patients with CGD diagnosed at Sultan Qaboos University Hospital (SQUH) were reviewed. Results: A total of 32 patients were diagnosed with CGD using molecular studies. Genetically confirmed individuals included 1 patient with XL-CGD (a large deletion involving the CYBB and XK genes resulting in a McLeod phenotype), 27 patients with AR-CGD with a c.579G>A (p.Trp193X) mutation at the NCF1 gene, and 4 patients with AR-CGD with a c.784G>A (p.Gly262Ser) mutation at the NCF1 gene. Flow cytometry and molecular results were available for comparison in 26 patients with AR-CGD. The patients with AR-CGD had a range of flow cytometry-generated fluorescent patterns as follows: reduced neutrophil stimulation with a sharp peak (12/26), reduced neutrophil stimulation with a broad peak (11/26), and a complete lack of neutrophil stimulation (3/26). No consistent flow cytometry-generated fluorescent pattern was observed in either of the 2 AR mutations identified in our patients. Conclusion: Flow cytometry is a robust test of CGD diagnosis. However, results should be interpreted with caution when predicting the underlying probable genotype, and results need to be complemented with definitive molecular studies.",
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