Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia
| Autor: | M. S. Abdelmoula, Jalel Chemli, Sonia Abdelhak, Fethi Mellouli, S. Boukthir, Z. Fitouri, Mohamed Bejaoui, Neji Tebib, K. Bouslama, Houda Elloumi-Zghal, M. K. Dellagi, Mohamed-Ridha Barbouche, S. M’Rad, H. Touiri, R. El Kares |
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| Rok vydání: | 2006 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Tunisia Genotype DNA Mutational Analysis Molecular Sequence Data Genes Recessive Consanguinity Biology Granulomatous Disease Chronic medicine.disease_cause Genetic Heterogeneity Chronic granulomatous disease hemic and lymphatic diseases Genetics medicine Humans Child Genetics (clinical) Mutation Splice site mutation Base Sequence Genetic heterogeneity Homozygote Haplotype Infant medicine.disease Disease gene identification Pedigree Haplotypes Child Preschool Female |
| Zdroj: | Journal of Human Genetics. 51:887-895 |
| ISSN: | 1435-232X 1434-5161 |
| DOI: | 10.1007/s10038-006-0039-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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