title: Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes.
abstract: Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and cannot produce superoxide anions. The most common form is caused by mutations in CYBB encoding gp91phox. We investigated 24 CGD patients and their families. Twenty-one mutations in CYBB were classified as X91(0), X91(+) or X91(-) variants according to cytochrome b (558) expression. Point mutations in encoding regions represented 50 % of the mutations found in CYBB, splice site mutations 27 %, deletions and insertions 23 %. Eight mutations in CYBB were novel leading to X91(0)CGD cases. Two of these were point mutations: c493G>T and a double mutation c625C>G in exon 6 and c1510C>T in exon 12 leading to a premature stop codon at Gly165 in gp91phox and missense mutations His209Arg/Thr503Ile respectively. Two novel splice mutations in 5'intronic regions of introns 1 and 6 were found. A novel deletion/insertion c1024_1026delCTG/insT results in a frameshift introducing a stop codon at position 346 in gp91phox. The last novel mutation was the insertion of a T at c1373 leading to a frameshift and a premature stop codon at position 484 in gp91phox. For the first time the precise size of two large mutations in CYBB was determined by array-comparative genomic hybridization and carriers' status were evaluated by multiplex ligation-dependent probe amplification assay. No clear correlation between clinical severity and CYBB mutations could be established. Of three mutations in CYBA, NCF1 and NCF2 leading to rare autosomal recessive CGD, one nonsense mutation c29G>A in exon 1 of NCF2 was new.
authors.affiliation: Chronic Granulomatous Disease Diagnosis and Research Centre (CDiReC), Pôle Biologie, CHU de Grenoble, Grenoble, 38043, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Martel
authors.forename: Michelle
authors.initials: M
authors.lastname: Mollin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Beaumel
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Brion
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
authors.forename: Véronique
authors.initials: V
authors.lastname: Satre
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vieville
authors.forename: Mary
authors.initials: M
authors.lastname: Callanan
authors.forename: Christine
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Alexandra
authors.initials: A
authors.lastname: Salmon
authors.forename: Anne
authors.initials: A
authors.lastname: Pagnier
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Cécile
authors.initials: C
authors.lastname: Bost-Bru
authors.forename: Laurence
authors.initials: L
authors.lastname: Eitenschenck
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.forename: Daniel
authors.initials: D
authors.lastname: Floret
authors.forename: Claire
authors.initials: C
authors.lastname: Galambrun
authors.forename: Hervé
authors.initials: H
authors.lastname: Chambost
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Blot
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubié
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pouessel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Drillon-Haus
authors.forename: Bernard
authors.initials: B
authors.lastname: Conrad
authors.forename: Klara M
authors.initials: KM
authors.lastname: Posfay-Barbe
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Havlicekova
authors.forename: Tamara
authors.initials: T
authors.lastname: Voskresenky-Baricic
authors.forename: Kelecic
authors.initials: K
authors.lastname: Jadranka
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Arriazu
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Garcia
authors.forename: Lamia
authors.initials: L
authors.lastname: Sfaihi
authors.forename: Lamia Sfaihi Ben
authors.initials: LS
authors.lastname: Mansour
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Stasia
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C527764:NCF2 protein, human