title: Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: an Italian multicenter study.
abstract: Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes fail to produce antimicrobial superoxide because NADPH oxidase activity is absent. In about 65% of the cases, the disease is due to mutations affecting the X-linked CYBB gene, encoding the gp91(phox) subunit of NADPH oxidase. We investigated 34 CGD male patients by DHPLC and direct sequencing. A mutation was found in the CYBB gene of 33 patients and 9 of these were novel: one non-sense mutation (c.1123 G>T), three missense mutations (c.58G>A; c.1076 G>C; c.1357 T>A), two splice site mutations (c.141+5G>T; c.142-1G>A), one duplication (c.42_45dupCATT), one deletion (c.184delT), and one rare deletion of two non-contiguous nucleotides (c.1287delT+c.1290delC). One patient had the most frequent GT homozygous deletion in exon2 of the NCF-1 gene encoding the p47(phox) subunit of NADPH oxidase. The carrier analysis was performed in 23 patients' mothers and 16 female relatives through molecular and FISH studies. No clear correlation between the severity of clinical symptoms and the type of mutation could be demonstrated. This study further supports the great heterogeneity of the disease and the notion that genetic analysis is a critical step in obtaining a definitive diagnosis for CGD.
authors.affiliation: Department of Public Health and Cellular Biology, Tor Vergata University, Rome, Italy.
authors.forename: Gigliola
authors.initials: G
authors.lastname: Di Matteo
authors.forename: Lucia
authors.initials: L
authors.lastname: Giordani
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ventura
authors.forename: Maria
authors.initials: M
authors.lastname: Chiriaco
authors.forename: Jan
authors.initials: J
authors.lastname: Blancato
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sinibaldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Dellepiane
authors.forename: Antonino
authors.initials: A
authors.lastname: Trizzino
authors.forename: Fausto
authors.initials: F
authors.lastname: Cossu
authors.forename: Roberto
authors.initials: R
authors.lastname: Rondelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Domenico
authors.initials: D
authors.lastname: De Mattia
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Martire
mesh_terms: D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases