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 gp91phox 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 p47phox 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1935-1941 |
| Number of pages | 7 |
| Journal | Molecular Immunology |
| Volume | 46 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jun 2009 |
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Keywords
- Chronic Granulomatous Disease
- CYBB
- Genotype-phenotype correlation
- Mutation analysis
- NADPH oxidase
ASJC Scopus subject areas
- Molecular Biology
- Immunology
Cite this
Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations : An Italian multicenter study. / Di Matteo, Gigliola; Giordani, Lucia; Finocchi, Andrea; Ventura, Annamaria; Chiriaco, Maria; Blancato, Jan; Sinibaldi, Cecilia; Plebani, Alessandro; Soresina, Annarosa; Pignata, Claudio; Dellepiane, Rosa Maria; Trizzino, Antonino; Cossu, Fausto; Rondelli, Roberto; Rossi, Paolo; De Mattia, Domenico; Martire, Baldassarre.
In: Molecular Immunology, Vol. 46, No. 10, 06.2009, p. 1935-1941.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations
T2 - An Italian multicenter study
AU - Di Matteo, Gigliola
AU - Giordani, Lucia
AU - Finocchi, Andrea
AU - Ventura, Annamaria
AU - Chiriaco, Maria
AU - Blancato, Jan
AU - Sinibaldi, Cecilia
AU - Plebani, Alessandro
AU - Soresina, Annarosa
AU - Pignata, Claudio
AU - Dellepiane, Rosa Maria
AU - Trizzino, Antonino
AU - Cossu, Fausto
AU - Rondelli, Roberto
AU - Rossi, Paolo
AU - De Mattia, Domenico
AU - Martire, Baldassarre
PY - 2009/6
Y1 - 2009/6
N2 - 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 gp91phox 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 p47phox 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.
AB - 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 gp91phox 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 p47phox 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.
KW - Chronic Granulomatous Disease
KW - CYBB
KW - Genotype-phenotype correlation
KW - Mutation analysis
KW - NADPH oxidase
UR - http://www.scopus.com/inward/record.url?scp=65549083114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65549083114&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2009.03.016
DO - 10.1016/j.molimm.2009.03.016
M3 - Article
C2 - 19410294
AN - SCOPUS:65549083114
VL - 46
SP - 1935
EP - 1941
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 10
ER -