Identification of a Novel Mutation of LAMB3 Gene in a Lybian Patient with Hereditary Epidermolysis Bullosa by Whole Exome Sequencing

No abstract available.

[Molecular exploration of the r91W [rPe65 gene] in Tunisian patients with early onset retinal Dystrophy and early onset retinis pigmentosa]

Background: Inherited retinal dystrophies are the major causes of blindness and visual impairment. Visual loss is due to neurosensory retinal and pigment epithelium cells degeneration. The most severe were Leber Congenital amaurosis [LCA], juvenile retinitis pigmentosa [RP] and early onset RP. The LCA and juvenile RP are called "Early Onset Retinal Dystrophy" [EORD]

Objective: Molecular exploration of the R91W [RPE65 gene] in Tunisian patients with Early Onset Retinal Dystrophy and early onset RP

Methods:All patients underwent a complete ophthalmological and a general examinations. The R91W exploration was performed by direct sequencing of exon 4 of the RPE65 gene and enzyme digestion

Results: Among 47 patients, 13 were from Nabeul. Twenty three had an EROD with a visual loss under the age of 2 years. Twenty four were with early onset RP and had these symptoms between the ages of 4 and 10 years. The best corrected visual acuity ranged from 2/10 to 1/60. Among the explored 94 chromosomes, the R91W [325C>T] allele was identified in heterozygous state in a sibling from Nabeul. The allele frequency was 2.12% [2/94]

Conclusion: All our patients had severe forms of RP with a decrease in visual acuity and a wide advanced retinal degeneration. The R91W mutation [325C>T] was not the major cause of EORD and early onset RP among Tunisian patients

Phenotype and mutational spectrum in Tunisian pediatric Gaucher disease

Gaucher disease [GD] is a sphingolipidosis with heterogeneous phenotypic expression. The vital and/or functional prognosis maybe threatened by an early visceral severe inolvement in type 1 or a neurological degeneration in the more rarest neuroneupathic forms. The phenotypic and genotypic data regarding Gaucher disease are poorly known in Maghrebian countries; they are even less for pediatric forms. The study is to highlight the specific phenotypic and genotypic changing among the widest Gaucher pediatric cohort in the Tunisian population. A restrospective study of a sample of children involved by gaucher disease. Twenty one cases of GD were identified, divided into 13 cases with type 1, 5 with type 3 and 3 children with acute neurological form. The first symptoms occurred before 1 year age in one third of patients with type 1GD. The clinical phenotype was severe according to the high severity score index and proportion of growth retardation. Portal hypertension was found in 8 patients. Three type 3 GD patients died before occurrence of the neurological signs. The phenotype was intermediate between the classic type 2GD and its perinatal lethal variant. Three patients were treated with enzyme replacement therapy and 4 others had allogenic bone marrow transplantation with a favorable outcome. Three mutations dominate the genotypic spectrum of GD in this cohort. Additionally to the N370 mutation, L444P and RecNcil mutations seem to occur more frequently compared to the GD forms presenting in adulthood. This data confirm the particular severity of Gaucher disease manifesting in childhood. This was enhanced through the high frequency of severe mutations. Further studies on largest cohort are needed to more clarify the phenotypic and genotypic features of Gaucher disease in Tunisia

[Lack of association between renin-angiotensin system [RAS] polymorphisms and hypertension in Tunisian type 2 diabetics]

The genes encoding renin-angiotensin system [RAS] components are potent candidate genes in both hypertension and diabetes namely ACE encoding the angiotensin converting enzyme and AGT encoding angiotensinogen. It has been suggested that the insertion/deletion [I/D] polymorphism in intron 16 of ACE gene is associated with ACE levels, and M235T gene polymorphism is associated with plasma AGT levels. We examined in this report the association between ACE I/D and AGT M235T polymorphisms with hypertension status in Tunisian type 2 diabetic subjects. Thirty nine hypertensive and 22 normotensive type 2 diabetic Tunisian patients were recruited for this study. The I/D polymorphism of ACE gene was analysed with nested PCR in order to avoid mistyping heterozygous individuals and the M235T polymorphism of AGT gene was analysed using PCR and allele specific restriction. The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without hypertension [DD: 49%; ID: 41%; II: 10% vs DD: 36%; ID: 55%; II: 9%, respectively] [lasmbda[2]= .06, p=0.5 8]. There was also no significant statistical difference between these two groups for the M235T polymorphism [TT: 20%; MT: 54%; MM: 26% vs TT: 27%; MT: 41%; MM: 32%, respectively] lambda[2]=0.95, p=0.62] RAS polymorphisms do not seem to play a role in the development of hypertension in the studied Tunisian type 2 diabetic subjects

[Influence of consanguinity on clinical characteristics and affective disorders frequency in relatives of bipolar I patients]

The genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from the existence of high rates of consanguinity. To determine the rate of consanguinity in bipolar I disorders sample and to compare the clinical characteristics and the frequency of affective disorders in first and second degree relatives of probands with and without consanguinity. One hundred thirty subjects met DSM-IV criteria for a bipolar I disorder were recruited. Available Information was obtained from a structured clinical interview, collateral history and medical records. The family investigation allowed completion of genealogies over three generations. The comparison was based on the clinical characteristics [age of onset, numbers of affective episodes, nature and severity of the last affective episode] and the frequency of affective disorders in first and second degree relatives of probands with and without consanguinity. The rate of consanguinity was estimated to 28, 5%It was higher in patients with family history of affective disorders: 34, 2%versus 20, 4%[p=0, 08]. Bipolar I patients with consanguinity were characterised by a high frequency of affective episodes and a more severe of the last affective episode, but theses differences were not significantly. However, the frequency of affective disorders was significantly increased in first degree relatives of probands with consanguinity: 10, 5%versus 6, 1%[p=0, 01], and in first and second degree relatives of probands with consanguinity: 4, 5%versus 2, 9%[p=0, 02]. The influence of consanguinity on the clinical characteristics and the frequency of affective disorders in first and second degree relatives of bipolar patients is en favour the recessive polygenetic transmission of bipolar disorders

Primary hyperoxaluria in children in central Tunisia

The goal of this work is to analyze clinical and therapeutics particularities of primary hyperoxaluria in children in Tunisian centre. We studied retrospectively 15 cases of primary hyperoxaluria enrolled during 9 years period [1994-2002]. It is about 2 boys and 13 girls [sex - ratio = 4.5] aged 2 month to 13 years [mean age: 4 years]. Six patients presented the infantile form and nine the juvenile form of HP. At the moment of diagnosis, renal function was normal in one patient, moderately altered in another and severely altered in the other patients. All patients had nephrocalcinosis and 6 among them radio-opaque renal calculi associated. Diagnosis of HP was established in 11 cases by hyperoxaluria and/or important hyperoxalemia or on the data of the renal biopsy and biochemical analysis of renal calculi in 4 cases. The so-called [maghrebin] mutation [Ile244Thr] sought-after in 9 children, has cannot be identified that in 2 among them. Eight patients died of the continuations of their illness. The seven other patients again in life present a terminal renal insufficiency treated by haemodialysis. No patient could benefit from organ transplantation. Primary hyperoxaluria is a very heterogeneous disease on the plan clinic that genetic. In Tunisia where it constitutes a frequent cause of end stage renal failure, prenatal diagnosis of this disease is of a big interest