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Title

Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes

Authors
Martel, Cécile
Mollin, Michelle
Beaumel, Sylvain
Brion, Jean Paul
Coutton, Charles
Satre, Véronique
Vieville, Gaëlle
Callanan, Mary
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Published in Journal of Clinical Immunology. 2012, vol. 32, no. 5, p. 942-58
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.
Keywords ChildChild, PreschoolFemaleGranulomatous Disease, Chronic/geneticsHumansInfantMaleMembrane Glycoproteins/geneticsMutationNADPH Oxidase/genetics
Identifiers
PMID: 22562447
Note Erratum : pp. 959-960
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Article (Published version) (60 Kb) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Groupe Posfay-Barbe Clara (pédiatrie générale) (853)
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MARTEL, Cécile et al. Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes. In: Journal of Clinical Immunology, 2012, vol. 32, n° 5, p. 942-58. https://archive-ouverte.unige.ch/unige:31691

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Deposited on : 2013-12-04

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