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 membranebound 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, DGT, 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.

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene

“…These findings further delineate the genetic heterogeneity of rare autosomal recessive diseases in Tunisia, as reported previously for different conditions. [22][23][24][25][26] Compared with the other two genes known to cause achromatopsia CNGA3 and CNGB3, GNAT2 is only a minor achromatopsia locus, which account for 2% of the cases. 7 As this is the largest sibship affected with GNAT2 achromatopsia, this family gave a unique opportunity for phenotype-genotype analysis and comparison to other complete achromatopsia subtypes.…”

Genetic Analysis of 10 Unrelated Korean Families with p22-phox-deficient Chronic Granulomatous Disease: An Unusually Identical Mutation of the CYBA Gene on Jeju Island, Korea

“…Although the prevalence of CGD may actually be higher than reported because of the under-diagnosis of milder phenotypes, the estimated prevalence of CGD is between 1 in 200,000 and 1 in 250,000 individuals, with variable occurrence in different countries (6-11). According to a collation by the Korean College of Pediatric Clinical Immunology, the prevalence of CGD from 2001 to 2005 in Korea was 0.9 in 1,000,000 individuals.…”

A novel mutation in NCF1 in an adult CGD patient with a liver abscess as first presentation

“…These were a 21-year old male with infections starting early in life that were not typical for CGD, thus postponing the correct diagnosis, a 22-year old female with infections starting early in life that were typical of CGD, 8 and a 20-year old male with unspecified infections. 10 Thus, the p47 phoxdeficient patient we describe here has the highest age at diagnosis reported thus far.…”