title: P67-phox (NCF2) lacking exons 11 and 12 is functionally active and leads to an extremely late diagnosis of chronic granulomatous disease (CGD).
abstract: Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000 + 2T → G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.
authors.affiliation: Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden, Germany. roeslerj@rcs.urz.tu-dresden.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Roesler
authors.forename: Florian
authors.initials: F
authors.lastname: Segerer
authors.forename: Henner
authors.initials: H
authors.lastname: Morbach
authors.forename: Stefan
authors.initials: S
authors.lastname: Kleinert
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thieme
authors.forename: Angela
authors.initials: A
authors.lastname: Rösen-Wolff
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Liese
mesh_terms: D057210:Delayed Diagnosis; D005091:Exons / Q000235:genetics*; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*
chemical_list: D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K