{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:56:00Z","timestamp":1772661360301,"version":"3.50.1"},"reference-count":15,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Public Policies and Models of Health Care - PMA","award":["PMA2019"],"award-info":[{"award-number":["PMA2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterized by impaired phagocyte function, recurrent fungal and bacterial infections and granuloma formation in multiple organs. Pediatric myelodysplastic Syndrome (MDS) is a rare hematological stem cell disease that leads to an ineffective hematopoiesis with variable risk of evolution to acute leukemias. Both disorders are rare and have distinct pathophysiologic mechanisms, with no known association. A 7-month-old boy presenting with recurrent infections and anemia at age 2 months underwent immunological, hematological and genetic investigation that culminated in the diagnosis of both CGD and MDS. Next generation sequencing was performed and identified a silent variant predicted as of Uncertain Significance, located in the splicing site at the end of exon 5 in CYBB. CYBB variants account for at least two thirds of CGD cases, but no previous descriptions of this variant were found in ClinVar or The Human Gene Mutation Database (HGMD) databases. We were able to demonstrate an exon 5 skipping on the proband\u2019s cDNA, which strongly suggests the disruption of the NADPH oxidase complex, abrogating the formation of reactive oxygen species from neutrophils. Moreover, erythroid cell lineage could be also affected by NADPH oxidase complex damages. Further investigation is needed to evaluate the potential effect of CYBB gene alterations in hematopoiesis, as well as in MDS and CGD association.<\/jats:p>","DOI":"10.3390\/genes12101476","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:59:15Z","timestamp":1632391155000},"page":"1476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Granulomatous Disease and Myelodysplastic Syndrome in a Patient with a Novel Mutation in CYBB"],"prefix":"10.3390","volume":"12","author":[{"given":"B\u00e1rbara C. S.","family":"Reis","sequence":"first","affiliation":[{"name":"Instituto Fernandes Figueira (IFF\/Fiocruz), Rio de Janeiro 22250-020, Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela P.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira (IFF\/Fiocruz), Rio de Janeiro 22250-020, Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula S.","family":"Bueno","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-610, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6135-4927","authenticated-orcid":false,"given":"Flavia A. A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira (IFF\/Fiocruz), Rio de Janeiro 22250-020, Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-5691","authenticated-orcid":false,"given":"Juliana","family":"Dutra","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira (IFF\/Fiocruz), Rio de Janeiro 22250-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana V.","family":"Mello","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-610, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-1099","authenticated-orcid":false,"given":"Maria Cec\u00edlia Menks","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-610, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane B.","family":"Milito","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine Sobral","family":"da Costa","sequence":"additional","affiliation":[{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-610, Brazil"},{"name":"Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-2224","authenticated-orcid":false,"given":"Zilton","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira (IFF\/Fiocruz), Rio de Janeiro 22250-020, Brazil"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/pai.12527","article-title":"Chronic Granulomatous Disease: Clinical, Molecular, and Therapeutic Aspects","volume":"27","author":"Chiriaco","year":"2016","journal-title":"Pediatr. 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