Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: An Italian multicenter study

Gigliola Di Matteo, Lucia Giordani, Andrea Finocchi, Annamaria Ventura, Maria Chiriaco, Jan Blancato, Cecilia Sinibaldi, Alessandro Plebani, Annarosa Soresina, Claudio Pignata, Rosa Maria Dellepiane, Antonino Trizzino, Fausto Cossu, Roberto Rondelli, Paolo Rossi, Domenico De Mattia, Baldassarre Martire

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)1935-1941
Number of pages7
JournalMolecular Immunology
Volume46
Issue number10
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Chronic Granulomatous Disease
  • CYBB
  • Genotype-phenotype correlation
  • Mutation analysis
  • NADPH oxidase

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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