Case Report

Skewed X-inactivation in a Female Carrier with X-linked Chronic Granulomatous Disease


Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocytic NADPH oxidase, causing a complete lack or significant decrease in the production of microbicidal reactive oxygen metabolites. It mainly affects male children; however, there are scarce reports of adult females diagnosed with X-linked-CGD attributed to an extremely skewed X-chromosome inactivation. This condition is characterized by severe and recurrent infections that usually develop after childhood. In clinical practice, physicians who usually confront these patients should suspect this entity and differentiate it from a secondary immunodeficiency. Here, we report a 38-year-old Mexican female with juvenile-onset X linked-CGD, caused by a de novo mutation and extremely skewed X-inactivation, whose clinical features were similar to those in patients with classic X-linked-CDG.

1. Gono T, Yazaki M, Agematsu K, Matsuda M, Yasui K, Yamaura M, et al. Adult onset X-linked chronic granulomatous disease in a woman patient caused by a de novo mutation in paternal-origin CYBB gene and skewed inactivation of normal maternal X chromosome. Intern Med 2008;47(11):1053-6.
2. Lewis EM, Singla M, Sergeant S, Koty PP, McPhail LC. X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation. Clin Immunol 2008;129(2):372-80.
3. Wolach B, Scharf Y, Gavrieli R, de Boer M, Roos D. Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB. Blood 2005;105(1):61-6.
4. Chollet-Martin S, Lopez A, Gaud C, Henry D, Stos B, El Benna J, et al. Severe X-linked chronic granulomatous disease in two unrelated females. Eur J Pediatr 2007;166(2):153-9.
5. Lun A, Roesler J, Renz H. Unusual late onset of X-linked chronic granulomatous disease in an adult woman after unsuspicious childhood. Clin Chem 2002;48(5):780-1.
6. Sarwar G, de Malmanche T, Rassam L, Grainge C, Williams A, Arnold D. Chronic granulomatous disease presenting as refractory pneumonia in late adulthood. Respirol Case Rep 2015;3(2):54-6.
7. Amaral JB, Paiva AA, Ramos FV, Stasia MJ, Lemos SG. X-linked chronic granulomatous disease in a female carrier with novel pathogenic mutation and skewed X-inactivation. Ann Allergy Asthma Immunol 2018;120(3):328-9.
8. Rosen-Wolff A, Soldan W, Heyne K, Bickhardt J, Gahr M, Roesler J. Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization. Ann Hematol 2001;80(2):113-5.
9. Marciano BE, Zerbe CS, Falcone EL, Ding L, DeRavin SS, Daub J, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol 2018;141(1):365-71.
10. Buduneli N, Baylas H, Aksu G, Kutukculer N. Prepubertal periodontitis associated with chronic granulomatous disease. J Clin Periodontol 2001;28(6):589-93.
11. Anderson-Cohen M, Holland SM, Kuhns DB, Fleisher TA, Ding L, Brenner S, et al. Severe phenotype of chronic granulomatous disease presenting in a female with a de novo mutation in gp91-phox and a non familial, extremely skewed X chromosome inactivation. Clin Immunol 2003;109(3):308-17.
IssueVol 18, No 4 (2019) QRcode
SectionCase Report(s)
Autoimmunity X-linked chronic granulomatous disease carrier Discoid lupus Skewed lyonization X-inactivation X-linked chronic granulomatous disease

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How to Cite
López-Hernández I, Deswarte C, Alcantara-Ortigoza M Ángel, Saez-de-Ocariz M del M, Yamazaki-Nakashimada MA, Espinosa-Padilla SE, Bustamante J, Blancas-Galicia L. Skewed X-inactivation in a Female Carrier with X-linked Chronic Granulomatous Disease. Iran J Allergy Asthma Immunol. 2019;18(4):447-451.