Chromosomal instability associated with a novel BLM frameshift mutation (c.1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome.

The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.

TCF7L2 is associated with type 2 diabetes in nonobese individuals from Tunisia.

The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele was associated with type 2 diabetes (T2D) in most populations worldwide. In individuals of European descent, the association with T2D was recently found to be modulated by obesity status. However, further studies are necessary to clarify if whether interaction exists among subjects of non-European descent. In the present study, we analyzed the association of rs7903146 with T2D in 90 nonobese (Body Mass Index [BMI] <25kg/m(2)), 171 overweight (25≤BMI<30kg/m(2)) et 98 obese (BMI≥30kg/m(2)) individuals from Tunisia. The T allele was nominally associated with T2D in nonobese subjects (Odds Ratio [OR]=3.24 [1.10-9.53], P=0.021) whereas no effect was detected in overweight (P=0.3) and obese (P=0.22) individuals. Consequently, the same risk allele decreased susceptibility to obesity in T2D subjects (OR=0.47 [0.23-0.94], P=0.029) but not in normoglycemic controls (P=0.44). When analyzed all together, no allelic association was observed with T2D (P=0.20) whereas an artefactual association with decreased obesity (0.59 [0.38-0.90], P=0.013) was detected. As in Europeans, TCF7L2 is therefore not a risk factor for obesity in Tunisians, but its effect on T2D risk is modulated by obesity. In conclusion, the TCF7L2 rs7903146 T allele is nominally associated with T2D susceptibility in nonobese individuals from Tunisia.

[Evaluation of the role of dietary intake in the occurrence of alopecia]. / Evaluation du rôle des apports alimentaires dans la survenue d'une alopécie diffuse.

Transversal case-control study was conducted among 42 patients aged between 20 and 35 years who had diffuse alopecia. Alimentary inquiry according to the 3-day method was achieved in each case. The following nutriments were evaluated: total proteins, calcium, copper, iron, iodine, magnesium, manganese, phosphorus, potassium, selenium, zinc, omega 3 and omega 6. A control group (composed of 230 individuals), matched for age, gender and metabolic profile was established. These persons did not suffer from hair and nail disorder. The nutriments were codified according to the data of the software Food processor 8.3 version. The data were analyzed using "SPSS" 11.5 version. Comparisons of the means were performed using the Student's t test. ROC graphics allowed to determine the statistically significative limits for the comparison of both groups. On multivariate analysis, only a protein intake was directly associated to alopecia, odds ratio of 1,5 (1,06 - 2,3) p=0,02.

WITHDRAWN: Effect of TCF7L2 polymorphism on the genetic susceptibility to obesity in the Tunisian population.

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Latent autoimmune diabetes in Tunisian adults (LADA): identification of autoimmune markers.

BACKGROUND: LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults. The aim of this study is to evaluate the frequency of autoimmmune markers and to identify patients with LADA among diabetics diagnosed initially as having type 2 diabetes. METHODS: Our study concerned 100 diabetics, aged between 31 and 77 years (age at onset > 30 years), with short term diabetes (duration < 6 years) and who required insulin therapy after 6 months from diagnosis of diabetes. All patients were screened for antibodies to Glutamic Acid Decarboxylase (GAD65), the Tyrosine Phosphatase (IA2) and Islet Cell antibodies (ICA). RESULTS: Mean age of patients is 53 +/- 10.5 years. Mean age at onset of diabetes was 43.3 +/- 10 years. Insulin treatment required after 3.1 +/- 1.8 years. Positivity of at least one of the auto-antibodies was found in 78% of patients. ICA were detected in 48.5% of cases. IA2 and GAD antibodies were positive respectively in 42% and 18% of tested patients. There was no significant difference of gender. Anti-GAD positive patients had statistically significant higher initial fasting blood glucose and HDL-cholesterol serum (p = 0.01 and 0.007) than those with anti-GAD negative. Patients with anti-IA2 were characterized by more important frequency of autoimmune diseases and low rate of triglycerides. The frequency of macrovascular complications was lower in ICA positive diabetics than those with ICA negative. Patients initially diagnosed as type 2 diabetes may in many cases suffer from LADA. Auto-antibodies screening may be of interest to identify LADA at the earliest stage. CONCLUSION: Frequency of type 1 diabetes in adults is underestimated. The identification of LADA may help to classify dabete and to indicate the moment of insulinotherapy.

[Retinal artery occlusion during disseminated lupus erythematosus]. / Occlusion artérielle rétinienne au cours d'un lupus érythémateux disséminé.

Retinal vascular disease in lupus is the most common ophthalmic manifestation, but retinal neovascularization is rare. We report a patient with sytemic lupus erythematosus and retinal neovascularization caused by branch retinal artery occlusion.

[Epibulbar osseous choristoma: two case reports]. / Ostéome épibulbaire: à propos de 2 cas.

INTRODUCTION: Epibulbar osseous choristoma is a congenital tumor consisting of normal tissue arising in an abnormal location. CARE REPORTS: We report two cases of epibulbar osseous choristoma discovered in 7- and 3-year-old girls. FIRST CASE: A calcified tumor was located regarding the temporal bulbar conjunctiva of the left eye. The rest of the ophthalmological examination was normal. Second case: During strabismus surgery, we unexpectedly discovered a white calcified mass located on the superior temporal part of the right eye. In both cases, a total excision was performed. Histopathological examination of the excised choristoma confirmed the diagnosis. DISCUSSION: Epibulbar osseous choristoma is a small unique nodule usually located on the superior temporal quadrant of the eye. Rarely reported in the literature, most cases are not recognized clinically and the diagnosis is essentially histopathological. CONCLUSION: Epibulbar osseous choristoma is a rare benign childhood tumor with an essentially histopathological diagnosis.

[Congenital coronary aneurysm. Report of two cases]. / Anevrysmes coronaires congenitaux. A propos de deux observations.

Congenital coronary aneurysms are an unusual anatomical entity. Their prognosis appears to be particularly dependent on the presence or absence of aneurysm thrombosis. We report two cases of congenital coronary aneurysms, diagnosed in one case after myocardial infarction. The two patients were treated successfully by an exclusion of the aneurysm and coronary bypass. The aim of this study is to discuss the clinical features, prognosis and management of this disease.

[The effect of nutritional education on the food intake regulation of the young diabetic]. / Incidence de l'education nutritionnelle sur la regulation de la prise alimentaire par le jeune diabetique.

The aim of our study is to evaluate the effect of nutritional education (applied during young diabetic camps) on the nutrition knowledge acquisition and the effective application of this knowledge by young diabetics in their dietary intake composition. This study included ten volunteers pupils, aged from 12 to 15 years. Each meal provided was quantified before and after consumption to determine during three consecutive days the exact amount of food consumed. Our results showed that the young diabetic could regulate his energetic intake in accordance with his needs. He didn't modify the proposed food when it was normocaloric (2615 +/- 390 Kcal), but he increased his food intake near the recommended needs when the proposed food was hypocaloric (1766 +/- 283 Kcal) and decreased his consumption when the proposed food was hypercaloric (4271 +/- 511 Kcal). Moreover, this study showed a significant negative correlation between the total energy intake and the amount of carbohydrates (r = -0.46, p < 0.01) and proteins (r = -0.70, p < 0.01), while it was positive between the first and lipid intake (r = 0.63, p < 0.01).

[Percutaneous mitral commissurotomy. 5-year results]. / La commissurotomie mitrale percutanee. Resultats a 5 ans.

Long-term results of percutaneous mitral commissurotomy were evaluated in 410 patients with mean age of 31 years (18 to 68 years). 48% of patients had mean thickened leaflets, 35% had calcified valves and 17% had flexible leaflets and subvalvular apparatus. Procedure was performed with a double balloon in 57% and with Inoue's balloon in 43% patients. A good immediate results was obtained in 77% of patients. A good result was defined as a mitral valve area > or = 1.5 cm2 without mitral regurgitation. Clinical follow-up concern 378 patients. The actuarial 5 years rate were 84% in our serie, without surgery or new percutaneous mitral commissurotomy and good functional results (NYHA class I or II) were 71%. Valvular anatomy, immediate results (mitral valve area), history of mitral commissurotomy, old patients, atrial fibrillation can influence strongly the results.

Undifferentiated pleomorphic sarcoma of the broad ligament.

AIMS: Sarcomas of the broad ligament are exceptionally rare. To our knowledge, the present case is the first description of undifferentiated pleomorphic sarcoma (UPS) occurring in the broad ligament. Herein, we report this unusual case, and discuss differential diagnoses and treatment. RESULTS: A 55-year-old postmenopausal woman was admitted for lower abdominal pain and vaginal spotting. Radiological examination revealed a latero-uterine mass that was independent of the surrounding organs. Treatment consisted in a total resection of the mass in addition to total abdominal hysterectomy and bilateral salpingo-oophorectomy. Based on histological examination, immunohistochemical study and quantitative PCR, a diagnosis of undifferentiated pleomorphic sarcoma (UPS) was made. The patient was lost to follow-up for 6 months, and then presented with a local recurrence of the tumour in addition to secondary pulmonary and vertebral localizations. The patient died less than one year after the first diagnosis. CONCLUSIONS: Diagnosis of UPS of the broad ligament is based on exclusion using a large panel of antibodies. There is no consensus for treatment. The prognosis of this disease cannot be assessed due to its rarity, but it can be hypothesized that early recurrence is indicative of poor prognosis.

[Factors associated with graft reepithelialization after penetrating keratoplasty]. / Les facteurs intervenant dans la réépithélialisation cornéenne après kératoplastie transfixiante.

INTRODUCTION: To study graft reepithelialization time after penetrating keratoplasty and the factors influencing this reepithelialization. PATIENTS AND METHODS: In this retrospective study, 48 patients underwent penetrating keratoplasty (52 eyes) by the same surgeon between 1998 and 2006. Recipient pre- and postoperative variables, donor characteristics, and surgical variables were analyzed. Postoperative slit-lamp examination after fluorescein staining and graft reepithelialization time were recorded. Statistical analysis was done using SPSS version 11.5 (p<0.05). RESULTS: The average graft reepithelialization time was 8.02 +/- 6.87 days. Complete corneal epithelial healing was obtained in 2.2%, 38.3%, and 63% of patients in 1, 3, and 7 days, respectively. There was a statistical correlation between graft reepithelialization time and trephination size, death-to-storage time, and storage time (p<0.05). DISCUSSION: Postoperative epithelial defects are common after penetrating keratoplasty. Many factors influence this graft reepithelialization such as abnormal lid and surface dysfunction, recipient corneal epithelium, and surgical technique. A better understanding of these factors will prevent postoperative epithelial defects and complications.

Effect of ENPP1/PC-1-K121Q and PPARgamma-Pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population.

Diabetes mellitus is the most common chronic metabolic disease. The raising diabetes epidemic is unfolding as an interaction between several environmental factors and a genetic predisposition. The aim of the current study was to evaluate the role of the PPARgamma-Pro12Ala and ENPP1-K121Q polymorphisms on type 2 diabetes (T2D) risk in a case-control study in the Tunisian population. To assess for any association of ENPP1-K121Q and PPARgamma-Pro12Ala polymorphisms with T2D risk, we analysed the genotypic and allelic distributions of each variant in the studied cohort. Our results support that the genetic variation at ENPP1-K121Q predisposes to T2D in the Tunisian population after adjustment on gender, age and BMI status (OR=1.55, 95%CI [1.11-2.16], p=0.007). Conversely, the PPARgamma-Pro12Ala variant seems not to have a significant effect on T2D risk in our Tunisian cohort. However, the minor A-allele would convey protection against overweight in the Tunisian population. In fact, the over weighted subjects showed a significantly lower frequency of A-allele than lean controls (OR=0.49, 95%CI [0.25-0.97], p=0.02). In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARgamma-12Ala allele may confer protection against overweight.

[Palpebral capillary hemangioma and amblyopia. Apropos of 2 cases]. / Hémangiome capillaire palpébral et amblyopie. A propos de 2 cas.

Periorbital capillary hemangiomas of childhood can produce visual axis occlusion and anisometropia, resulting in amblyopia. We report our experience performing surgical resection of periorbital capillary hemangiomas. Partial resection of hemangiomas was performed in two infants under five months of age, and permitted clearing of the visual axis. This immediate effect is necessary to prevent amblyopia. Surgical resection should be considered a treatment option for managing periorbital capillary hemangiomas which threaten vision.

HLA polymorphism in type 1 diabetes Tunisians.

Several studies of the association between HLA and type 1 diabetes have been carried out revealing differences between ethnic groups. Our study, as part of the studies that should be performed about this association in the rest of the word, aims at elucidating the HLA DRB1, DQB1 polymorphism in Tunisian type 1 diabetes. This study includes 43 unrelated type 1 diabetes patients, and their mean age at onset is less than 15 years. Analysis of the frequency of alleles and haplotypes in these subjects, compared to a reference group (n = 101) led to the following results. 1) The Tunisian insulin-dependent diabetics present similarities as well as differences with other ethnic groups (Caucasians, North Africans). 2) The haplotype DRB1*04 DQ*0302 and DRB1*03 DQB1*0201 is positively associated to type 1 diabetes. 3) The heterozygotic genotype DRB1*04 DQB1*0302 / DRB1*03 DQB1*0201 is strongly associated to type 1 diabetes. 4) The haplotypes DRB1*01501 DQB1*0602 and DRB1*11 DQB1*0301 proved to be protective. In addition, the study of the subtypes DRB1*04 showed that alleles DRB1*0405 predispose to type 1 diabetes, whereas the allele DRB1*0403, which is in linkage disequilibrium with the DQB1*0402 in the Tunisian population, has a protective effect.