Genetics and genomic medicine in Tunisia.

Genetics and genomic medicine in Tunisia. [Image: see text]

Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper IgM 2 patient retained mutagenic activity on SHM artificial substrate.

Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID.

A 1,100-year-old founder effect mutation in IL12B gene is responsible for Mendelian susceptibility to mycobacterial disease in Tunisian patients.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder predisposing apparently healthy individuals to infections caused by weakly virulent mycobacteria such as bacille Calmette-Guerin (BCG), environmental mycobacteria, and poorly virulent Salmonella strains. IL-12p40 deficiency is the first reported human disease due to a cytokine gene defect and is one of the deficiencies that cause MSMD. Nine mutant alleles only have been identified in the IL12B gene, and three of them are recurrent mutations due to a founder effect in specific populations.

Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds.

Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation.

Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients.

Objective: The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population.

Design: A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals.

[Homozygous antithrombin type HBS deficiency; a family study].

Congenital antithrombin (AT) deficiency is the most thrombotic genetic abnormality of haemostasis. Total quantitative deficits are lethal as early as life intra-uterine. Only homozygous mutations concerning the heparin-binding site are compatible with life.

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

[Association study between diabetic retinopathy and aldose reductase gene polymorphism in Tunisians].

Introduction: Aldose reductase (ALR2), the enzyme of the polyol pathway, may play an important role in the pathogenesis of diabetic microvascular complications, namely diabetic retinopathy. The study aimed to determine whether the aldose reductase gene is involved in diabetic retinopathy in the Tunisian population.

Material: and methods: A case-control study was conducted in 47 type 2 diabetic patients who have diabetic retinopathy and 28 diabetic patients without diabetic retinopathy in spite of diabetes lasting for more than 5 years and over 10 years in 13 cases.

Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guérin infection.

Five patients from 4 unrelated Tunisian families who presented with disseminated neonatal infection by Mycobacterium bovis bacille Calmette-Guérin strain were investigated. Two unrelated patients had different homozygous interleukin-12 receptor beta1 subunit gene splice-site mutations (64+5G-->A and 550-2A-->G). Two siblings and 1 unrelated patient, all of whom were from the same town, carried the same mutation (297del8) within the interleukin-12p40 gene.