Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia.

J Hum Genet 2006 26;51(10):887-95. Epub 2006 Aug 26.

Molecular Investigation of Genetic Orphan Diseases Research Unit, MIGOD, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis, Tunisia.

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.

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December 2006
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References

(Supplied by CrossRef)
Article in Acta Paediatr
A Ahlin et al.
Acta Paediatr 1995
Article in Blood
BM Babior et al.
Blood 1999
Article in Science
RL Baehner et al.
Science 1967
Article in Presse Med
MR Barbouche et al.
Presse Med 1999
Article in Proc Natl Acad Sci USA
CM Casimir et al.
Proc Natl Acad Sci USA 1991
Article in Blood Cells Mol Dis
SJ Chanock et al.
Blood Cells Mol Dis 2000
Article in N Engl J Med
RA Clark et al.
N Engl J Med 1989
Article in Blood Cells Mol Dis
AR Cross et al.
Blood Cells Mol Dis 2000
Article in Nature
C Dib et al.
Nature 1996
Article in Annu Rev Med
MC Dinauer et al.
Annu Rev Med 1992
Article in Nature
MC Dinauer et al.
Nature 1987

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