title: Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia.
abstract: NADPH oxidase, a multi-subunit protein consisting of cytosolic components and the membrane-bound heterodimer, plays an instrumental role in host defence mechanisms of phagocytes. Genetic deficiency of the enzymatic complex results in an inherited disorder, chronic granulomatous disease (CGD), which is characterized by an impaired phagocyte microbicidal activity. X-Linked (XL) CGD results from a mutation in the CYBB gene encoding the gp91phox subunit, while autosomal recessive (AR) CGD is associated with mutations in one of the NCF1, NCF2 and CYBA genes that encode the p47phox, p67phox and p22phox subunits, respectively. In the study reported here, we investigated genetic defects underlying CGD in 15 Tunisian patients from 14 unrelated families. Haplotype analyses and homozygosity mapping with microsatellite markers around known CGD genes assigned the genetic defect to NCF1 in four patients, to NCF2 in four patients and to CYBA in two patients. However, one family with two CGD patients seemed not to link the genetic defect to any known AR-CGD genes. Mutation screening identified two novel mutations in NCF2 and CYBA in addition to the recurrent mutation, DeltaGT, in NCF1 and a splice site mutation previously reported in a North African patient. Our results revealed the genetic and mutational heterogeneity of the AR recessive form of CGD in Tunisia.
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases Research Unit (MIGOD), Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis, Tunisia.
authors.forename: R
authors.initials: R
authors.lastname: El Kares
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: M R
authors.initials: MR
authors.lastname: Barbouche
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Elloumi-Zghal
authors.affiliation: Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Service de Pédiatrie, Centre Hospitalo-Universitaire Sahloul, Sousse, Tunisia.
authors.forename: J
authors.initials: J
authors.lastname: Chemli
authors.affiliation: Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia.
authors.forename: F
authors.initials: F
authors.lastname: Mellouli
authors.affiliation: Service de Pédiatrie, Hôpital La Rabta, Tunis, Tunisia.
authors.forename: N
authors.initials: N
authors.lastname: Tebib
authors.affiliation: Service de Pédiatrie, Hôpital La Rabta, Tunis, Tunisia.
authors.forename: M S
authors.initials: MS
authors.lastname: Abdelmoula
authors.affiliation: Hôpital d'Enfants, Tunis, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: Boukthir
authors.affiliation: Hôpital d'Enfants, Tunis, Tunisia.
authors.forename: Z
authors.initials: Z
authors.lastname: Fitouri
authors.affiliation: Hôpital Mongi Slim, La Marsa, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: M'Rad
authors.affiliation: Hôpital Mongi Slim, La Marsa, Tunisia.
authors.forename: K
authors.initials: K
authors.lastname: Bouslama
authors.affiliation: Service des maladies infectieuses, Hôpital La Rabta, Tunis, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Touiri
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases Research Unit (MIGOD), Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis, Tunisia. sonia.abdelhak@pasteur.rns.tn.
authors.forename: S
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: M K
authors.initials: MK
authors.lastname: Dellagi
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D014416:Tunisia