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Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease

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Abstract

Purpose

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019.

Methods

Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds.

Results

Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0–186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations.

Conclusions

The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

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Acknowledgments

We thank the patients and their families for their collaboration.

Funding

The CONACYT-SALUD-2012-01-180910 and FUMENI A.C. supported this project. LBG, SEP, and MAYN have SNI-CONACYT fellowships. The protocol was approved (number 019/2011) at National Institute of Pediatrics Research and Ethics Committees. The Laboratory of Human Genetics of Infectious Diseases is supported by the Rockefeller University, The Foundation for Medical Research (FRM), the St. Giles Foundation, the French National Institute of Health and Medical Research (INSERM), Paris University, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), and the French National Research Agency under the “Investments for the future” program (grant number ANR-10-IAHU-01), ANR-GENMSMD (grant number ANR-16-CE17-0005-01 for JB).

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Correspondence to Lizbeth Blancas-Galicia or Jacinta Bustamante.

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Informed consent for participation in this study was obtained in accordance with local regulations, with approval from the IRB. The experiments described here were performed in Mexico and France, in accordance with local regulations.

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Written informed consent was obtained from the guardians of the pediatric patients or directly from adult patients.

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Blancas-Galicia, L., Santos-Chávez, E., Deswarte, C. et al. Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease. J Clin Immunol 40, 475–493 (2020). https://doi.org/10.1007/s10875-020-00750-5

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