A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family.

Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized.

Evaluation of resistance to temephos insecticide in Culex pipiens pipiens larvae collected from three districts of Tunisia.

BACKGROUND: Mosquitoes are considered as the main groups of arthropods that cause nuisance and public health problems. OBJECTIVES: Evaluation of resistance to temephos insecticide in Culex pipiens pipiens larvae collected from three districts of Tunisia. METHODS: Late third and early fourth instars larvae of Culex pipiens pipiens were collected in three localities of Northern and Southern Tunisia. Field collected populations were tested against temephos insecticide and compared to bioassays of a susceptible reference strain. The cross-resistance between temephos and propoxur, and the polymorphism of over-produced esterases and AChE 1 were investigated. RESULTS: Studied populations exhibited tolerance to temephos with low and high levels of resistance. The resistance ratio (RR50) values of temephos ranged from 1.34 to 114. Synergists and starch electrophoresis showed that the metabolic resistances were involved in the recorded resistance. Likewise, the resistant target site (acetyl cholinesterase: AChE 1) was responsible for the recorded resistance to temephos compound in Culex pipiens pipiens. CONCLUSION: The low and high resistance recorded to temephos insecticides is particularly interesting, because it leaves a range of tools useable by vector control services. However, further studies are needed to determine its spread and anticipate vector control failure where these insecticides are used.

The potential role of urbanization in the resistance to organophosphate insecticide in Culex pipiens pipiens from Tunisia.

OBJECTIVE: To examine the effects of urbanization on the resistance status of field populations of Culex pipiens pipiens to organophosphate insecticide. METHODS: Bioassays and biochemical assays were conducted on Tunisian field populations of Culex pipiens pipiens collected in four various areas differing in the degree of urbanization. Late third and early fourth larvae were used for bioassays with chlorpyrifos and adults mosquitoes for biochemical assays including esterase and acetyl cholinesterase (AChE) activities. RESULTS: The distribution of resistance ratios in this study appears to be influenced by the degree of urbanization. The highest resistance was recorded in the population from most urbanized areas in Tunisia whereas the lowest resistance was found in relatively natural areas. Both metabolic and target site mechanisms were involved in the recorded resistance. CONCLUSION: This is the first study in Tunisia showing evidence of the impact of urbanization on the resistance level in Culex pipiens pipiens. Proper management of the polluted breeding sites in the country and effective regulation of water bodies from commercial and domestic activities appear to be critical for managing insecticide resistance.

Resistance to pyrethroid insecticides in Culex pipiens pipiens (Diptera: Culicidae) from Tunisia.

Resistance toward 2 pyrethroïd insecticides (permethrin and deltamethrin), and an organochloric one (DDT) was analyzed in 18 samples of Culex pipiens pipiens common mosquitoes collected from different Tunisian areas between March 2002 and November 2005. Bioassays were performed over different larvae samples. The recorded mortalities, after 24h exposure to increased doses of insecticides, were compared to those obtained on a susceptible reference strain (S-LAB). All samples were resistant to permethrin. However, a large variation in the tolerance to this insecticide was observed between samples. Resistance ratio levels at LC50 (RR50) for the analyzed samples were ranged from 1.5 to 9092 folds. For deltamethrin, 14 among 17 studied samples were resistant. RR50, in the resistant samples, were ranged from 3 to 453 folds. Resistance to the two tested pyrethroids and DDT were correlated. The use of synergists showed that the cytochrome P450-dependent monooxygenases had a major contribution to the permethrin and deltamethrin resistance and that the esterases (and/or glutathione-S-transferases) had only a minor contribution. Results were discussed in relation to resistance mechanisms and mosquito's control.

Resistance status to deltamethrin pyrethroid of Culex pipiens pipiens (Diptera: Culicidae) collected from three districts of Tunisia.

OBJECTIVES: The aim of the present study was to determine the susceptibility status of Culex pipiens pipiens populations against deltamehtrin insecticide. METHODS: Larvae of Culex pipiens pipiens were collected from three breeding places in Northern and Southern Tunisia between 2003 and 2005. Early third and late fourth instars were tested against deltamethrin pyrethroid insecticide. Cross-resistance with DDT resistance was evaluated in studied samples to estimate the role of target site insensitivity and two synergists including piperonyl butoxide (Pb) and S,S,S-tributyl phosphorotrithioate (DEF) were used to estimate the role of detoxification enzymes. RESULTS: Our results revealed that the level of deltamehtrin resistance ranged from 0.67 to 31.4. We also showed the non-involvement of kdr resistance in pyrethroid resistance and no cross-resistance with DDT resistance was detected in all studied populations including the most resistant one. Synergists study on the resistant population (sample # 1) showed the involvement of CYP450 in the recorded resistance to the deltamethrin insecticide. CONCLUSION: The results obtained from this study should be considered in the current control programs to combat mosquitoes in Tunisia.