Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

Intravitreal bevacizumab versus photodynamic therapy for myopic choroidal neovascularization in a North-African population.

PURPOSE: To compare the 1-year functional and anatomical outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy (PDT) in patients with myopic choroidal neovascularization (CNV). METHODS: Review of retrospectively collected data of 80 eyes in 80 patients with myopic CNV treated with standard PDT (n = 40) or IVB (1.25 mg/ 0.05 ml) (n = 40). Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured with optical coherence tomography (OCT) were compared between the two groups at baseline, 3, 6 and 12 months. RESULTS: In the IVB group, mean BCVA was +0.9 ± 0.85 logMAR at baseline. Mean BCVA was significantly better at 3 and 6 months than baseline (p = .0095 and p = .008, respectively) but not at 12 months (p = .065). In the PDT group, mean BCVA was +0.88 ± 0.45 logMAR at baseline, and improved to +0.85 ± 0.62 logMAR at 3 months and to +0.86 ± 0.44 logMAR at 6 months, which was not significantly different from baseline. Mean BCVA then decreased to +0.9 ± 0.54 logMAR at 12 months (p = .85). Mean logMAR VA was significantly better in the IVB group than in the PDT group after 3 months (p = .0043), 6 months (p = .0001) and 12 months (p = .0168). Mean CRT was significantly lower in IVB group than in PDT group at 3, 6 and 12 months (p = .008, p = .038, p = .040, respectively). Chorioretinal atrophy developed in six eyes (15%) treated with IVB and in 24 eyes (60%) treated with PDT at 12 months (p = 3.2 × 10(-5)). CONCLUSIONS: Over a 12-month period, intravitreal bevacizumab seems to be superior to photodynamic therapy in controlling myopic CNV in a North-African population.

[Orbital cellulitis and endophthalmitis after cataract surgery]. / Cellulite orbitaire avec endophtalmie après chirurgie de cataracte.

Orbital cellulitis with endophthalmitis is an extremely uncommon complication following ocular surgery. We report the case of 38 year-old man who developed orbital cellulitis and endophthalmitis after extracapsular extraction and posterior chamber implant placement for cataract secondary to radiotherapy. Phacoextraction was performed under general anaesthesia and was uneventful. Three days postoperatively, the patient was examined for a reduced visual acuity and lid swelling in the operated eye. Ocular examination has shown signs of endophthalmitis and orbital cellulitis, which was confirmed by a computed tomographic scan. Bacteriology cultures were positive for a Streptococcus pneumoniae. The ocular infection evolved towards phthisis bulbi with no light perception 45 days after surgery. Enucleation with orbital implant was performed.

Coexistence of mal de Meleda and congenital cataract in a consanguineous Tunisian family: two case reports.

INTRODUCTION: Mal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts. CASE PRESENTATION: A Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family. CONCLUSION: To the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda.