Abstract
Chronic granulomatous disease (CGD) is caused by a defect in both the host's defenses and its regulation of inflammation normally provided by phagocytes and other leukocytes. As in the case described here, it is not uncommon that CGD patients are diagnosed late, only after organ-damaging manifestations have already progressed. In this patient, we found that CGD arose due to a splice-supporting mutation in the last position of a cryptic exon towards the middle of intron 6 of the CYBB (gp91-phox) gene. The mutation led to the insertion of 56 bp into most of the CYBB mRNA of leukocytes causing a frame shift and a premature stop codon. The normal cryptic exon was also found to be mildly active in some tissues other than leukocytes in healthy donors, to be conserved in many primates, and to a lesser degree in other mammals. Some sequence similarity suggests that the cryptic exon may have originated from a mammalian interspersed repetitive (MIR) element. Taken together, we clarify an unusual disease-causing mutation, indicate its evolutionary background and emphasize the importance of a timely diagnosis of CGD.
References
Sep 1, 1992·Human Genetics·M KrawczakD N Cooper
Jan 1, 1991·European Journal of Pediatrics·J RoeslerA Emmendörffer
Aug 7, 1990·Journal of Immunological Methods·A EmmendörfferJ Roesler
Aug 11, 1995·Nucleic Acids Research·J P Murnane, J F Morales
Sep 15, 1994·Cytometry·A EmmendörfferJ Roesler
Jun 1, 1993·Clinical Immunology and Immunopathology·J T Curnutte
Oct 23, 1997·The Journal of Clinical Investigation·A GörlachJ T Curnutte
Oct 24, 1997·International Archives of Allergy and Immunology·A D CrockardC P Turner
Mar 25, 1999·Experimental Hematology·J RoeslerA Rösen-Wolff
Dec 22, 1999·Human Genetics·D NoackP G Heyworth
Feb 1, 2000·Trends in Genetics : TIG·D C Hughes
Jun 9, 2000·Medicine·B H SegalS M Holland
Feb 13, 2001·Blood Cells, Molecules & Diseases·P G HeyworthA R Cross
Mar 23, 2001·Annals of Hematology·A Rösen-WolffJ Roesler
Nov 19, 2003·Genetical Research·J C SilvaA S Kondrashovi
Dec 9, 2003·Neuromuscular Disorders : NMD·Christophe BéroudFrance Leturcq
Dec 31, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Mindy Anderson-CohenJoachim Roesler
Mar 18, 2005·Annual Review of Immunology·Anthony W Segal
Dec 21, 2005·Journal of Evaluation in Clinical Practice·Joachim RoeslerAngela Rösen-Wolff
Citations
Oct 14, 2009·Human Genetics·Igor Vorechovsky
May 7, 2011·Antioxidants & Redox Signaling·Michael Li-Hsuan HuangDes R Richardson
Jul 21, 2006·Nucleic Acids Research·Emanuele BurattiFrancisco E Baralle
Nov 30, 2006·Current Opinion in Hematology·Harry L Malech, Dennis D Hickstein
May 17, 2007·Shock·Zoltán Spolarics
Nov 10, 2013·International Journal of Cell Biology·Maurizio RomanoDiana Baralle
Aug 24, 2010·Blood Cells, Molecules & Diseases·Dirk RoosJohn I Gallin
Jan 20, 2010·The FEBS Journal·Ashish Dhir, Emanuele Buratti
Feb 29, 2008·American Journal of Human Genetics·Fanny MochelRonald G Haller
Nov 29, 2017·Frontiers in Immunology·Zoltan SpolaricsDavid H Livingston
Sep 15, 2007·British Journal of Haematology·Silvia SpenaMaria Luisa Tenchini
Mar 27, 2007·Clinical Chemistry·Lysann MauchJoachim Roesler
Dec 20, 2018·Frontiers in Immunology·Jesse BruijnesteijnRonald E Bontrop
Apr 1, 2020·F1000Research·Giorgia Bucciol, Isabelle Meyts
May 13, 2017·Human Genetics·Rita Vaz-DragoMaria Carmo-Fonseca
May 11, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Dirk Roos, Martin de Boer