A non-syndrome form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q.

Non-syndromic, recessively inherited deafness is the most predominant form of severe inherited childhood deafness. Until now, no gene responsible for this type of deafness has been localized, due to extreme genetic heterogeneity and limited clinical differentiation. Linkage analyses using highly polymorphic microsatellite markers were performed on two consanguineous families from Tunisia affected by this form of deafness. The deafness was profound, fully penetrant and prelingual. A maximum two-point lod score of 9.88 (theta = 0.001) was found with a marker detecting a 13q locus (D13S175). Linkage was also observed to the pericentromeric 13q12 loci D13S115 and D13S143. These data map this neurosensory deafness gene to the same region of chromosome 13q as the gene for severe, childhood autosomal recessive muscular dystrophy.

HLA class II polymorphisms in Tunisian patients with dilated cardiomyopathy.

Cardiomyopathies (CMs) are primary disorders of cardiac muscle. They are a major cause of morbidity and mortality for all ages and, like acquired forms of cardiovascular disease, often result in heart failure. Molecular genetic studies have made remarkable progress in defining the pathogenesis of CM. The present study was the first report to evaluate the relationship between class II major histocompatibility complex (MHC) genes (HLA-DRB1 and HLA-DQB1) and the genetic susceptibility to primary dilated cardiomyopathy (DCM) in Tunisian patients. The human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed in 76 patients with primary DCM and 111 ethnically matched healthy controls using polymerase chain reaction-sequence specific primers technique. An increased frequencies of HLA-DRB1*0401 (OR = 2.67, P < 0.001), HLA-DQB1*0302 (OR = 3.28, P = 0.001) and HLA-DQB1*0401 (OR = 6.26, P = 0.005) alleles were found in the patients with primary DCM compared with healthy controls. Individuals with HLA-DRB1*1301 (OR = 0.24, P < 0.001) and HLA-DQB1*0201 (OR = 0.49, P = 0.002) alleles have a protective effect against primary DCM. Two haplotypes were associated with increased risk of primary DCM: DRB1*0401/DQB1*0302 (OR = 4.53, P = 0.002) and DRB1*0401/DQB1*0401 (OR = 9.42, P = 0.004). In conclusion, our data suggest that the variation in class II HLA alleles could be a genetic factor involved in the susceptibility to primary DCM in the Tunisian population.

[Otosclerosis in populations living in northern Tunisia: epidemiology and etiology]. / L'otospongiose dans les populations du nord de la Tunisie: épidémiologie et étiologie.

Otosclerosis is a hereditary disease frequently encountered in Caucasian populations (0.1 to 2% prevalence). In Tunisia, prevalence varies from 0.4% to 0.8%. The presence of a genetic factor associated with hormonal, biochemical or environmental factors, probably lead to variable expression of the otosclerosis according to age and sex. Mean age at onset of disease is 25 years (range 16-35 year) for 61.5% of affected women. In men this proportion is 50.2%. The incidence of otosclerosis is high in the 26-35 year age group. Our study showed that in northeastern areas of Tunisia, women in this age group were affected twice as often as men in this age group. This probably suggests that an endocrine mechanism is involved in disease etiology. However, in northwestern areas, there was no significant difference between the rates of otosclerosis between sexes. Geographical distribution of affected subjects according to the ethnic origin of their parents showed that the areas with the highest concentration of affected individuals were urban or seaside areas such as the gouvernorate of Nabeul. The frequency of otosclerosis was lower in rural areas and/or areas far from the seaside.

[Epidemiological study of the idiopathic dilated cardiomyopathy in Tunisia]. / Étude épidémiologique de la cardiomyopathie dilatée idiopathique en Tunisie.

AIMS OF THE STUDY: Idiopathic dilated cardiomyopathy (IDC) is a complex disease. The interest of this study were to investigate the epidemiology characteristics of the disease and to evaluate the prognostic echocardiographic markers by region in order to highlight the existence of genetic risk factors and/or environmental and to identify those patients who could benefit from early treatment and better care to avoid further complications of the disease. PATIENTS AND METHODS: This is a retrospective study based on the Fischer exact and bilateral Mann-Whitney test. RESULTS: We included 526 patients with dilated cardiomyopathies of them we detected 50 cases of IDC including 12 families: The average age was 39,3±15.2 years. The sex ratio was 2.6. Mean left ventricular end-diastolic diameter (DIVGd) was higher in patients from the North East region (44.3±6.2mm/m(2)). Using Receiver Operating Characteristics (ROC) curve, we found a threshold value of 40mm/m(2). The odds ratio associated with this cutoff was 9.2. CONCLUSION: Our results suggest that the prevalence and severity of IDC were higher in the North East region of Tunisia. Furthermore, large-scale prospective studies are needed to confirm these findings. In confirmation of a higher prevalence, a genetic study should be undertaken in this region.

A genetic study of otosclerosis in a population living in the north of Tunisia.

The frequency of otosclerosis has been estimated to be 0.6 per 100 inhabitants in a population living in the North of Tunisia. The sex ratio in probands is 0.73 with clinical otosclerosis being approximately twice as frequent in females than in males, an observation which could be due to hormonal factors. The main risk period for otosclerosis is between 25 and 35 years of age in both sexes. Segregation analysis was performed in 193 nuclear families belonging to 65 pedigrees of otosclerosis. The pattern of the disease is due to a rare dominant major gene with a high polygenic component. This finding was unexpected since otosclerosis is usually considered to be a disease with simple dominant inheritance and incomplete penetrance. The authors have estimated that only 13% of affected patients are carriers of the rare dominant gene. This gene has strong penetrance which, however, varies according to age and sex.

Genetic heterogeneity study of non-syndromic autosomal recessive sensorineural deafness within the Tunisian population.

The number of loci for non-syndromic autosomal recessive sensorineural (N-SARS) deafness, was estimated within the Tunisian population and compared to that obtained in other populations. 30 deaf couples have been collected from 4 governorates (2,318,900 inhabitants) and 3 villages. Our investigations in these regions show that the percentage of congenitally deaf persons which marry each other is exceptionally low (10-30%). The number of loci for N-SARS deafness in the governorates sample was estimated at 8.3. Results could provide data for genetic counseling and facilitate our research concerning the localization of the different loci for N-SARS deafness present in Tunisian population.

An epidemiological and genetic study of congenital profound deafness in Tunisia (governorate of Nabeul).

An epidemiological and genetic study of profound deafness has been undertaken in the governorate of Nabeul in Tunisia. This paper deals with sensorineural deafness with no associated abnormalities. The prevalence was estimated to be 0.0007 and four clusters could be identified, two of which represent 51% and 34% respectively of the total number of cases. Segregation analysis performed in 29 pedigrees containing 415 subjects with 129 affected cases provided evidence for simple recessive inheritance with no sporadic cases.

Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates.

Geographically isolated populations have been successfully used to localize genes for recessive inherited diseases, including non-syndromic sensorineural recessive deafness (NSRD). To date, 25 loci for NSRD have been localized on human chromosomes (DFNB loci), and six of the corresponding genes have been identified. Here, we report on the contribution of the DFNB1 locus (GJB2 gene) to NRSD in seven affected families living in three northern Tunisian geographic isolates, and we provide evidence for genetic heterogeneity within isolates. This finding challenges the classical view of a single 'founder' mutation segregating in such isolates.