Nucleic acid spot hybridization with nonradioactive labeled probes in screening for human papillomavirus DNA sequences

We examined 161 human tissue samples using the spot hybridization technique with nonradioactive labeled DNA probes of human papillomavirus (HPV). Whole cells were spotted on nitrocellulose filters; DNA of the cells was denatured and fixed to the filter. Then the DNA spots were hybridized to nonradioactive labeled DNA and monitored by a sandwich immunoenzymatic reaction. This technique is simple, sensitive, specific, requires no special equipment, and can be used in clinical settings. HPV DNA was found in 92% of samples in which, on the basis of histologic and colposcopic criteria, its presence was suspected, as well as in 31 samples where it was not suspected.     

Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I

Recently, a spinal muscular atrophy (SMA) determining gene, termed survival motor neuron (SMN) gene, has been isolated from the 5q13 region and found deleted in most patients. A highly homologous copy of this gene has also been isolated and located in a centromeric position. We have analyzed 158 patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%. Mutations other than gross deletions seem to be extremely rare. In one of the undeleted SMA type I patients, a newborn who survived for only 42 days, we detected a maternally inherited 5 bp microdeletion in exon 3, resulting in a premature stop codon. By RT-PCR and long range PCR amplification we were able to show that the deletion belongs to the SMN gene, rather than to the centromeric copy, and that the proposita had no paternal SMN gene. Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which maps close to SMN and has been proposed as a SMA modifying gene, suggests the presence of at least one full-length copy. Haplotype analysis of closely linked polymorphic markers suggests that the proposita also lacks the maternally derived copy of the centromeric homologue of SMN supporting the hypothesis that the severity of the phenotype might depend on the reduced number of centromeric genes in addition to the frameshift mutation.      

CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma

Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for <5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family.

Objective: To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation.

Methods and subjects: CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls.

Results: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13–52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG.

Conclusion: CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.

     

SMN gene analysis of the spinal form of Charcot-Marie-Tooth disease.

The spinal form of Charcot-Marie-Tooth disease (spinal CMT) is a rare genetic disorder of the peripheral nervous system, the genetic basis of which remains unknown. To test the hypothesis that a defect of survival motor neuron (SMN), the determining gene for spinal muscular atrophy (SMA), would result in spinal CMT, 18 unrelated spinal CMT patients were studied. Nine of them were sporadic cases and the other nine belonged to unrelated autosomal dominant pedigrees. None of the 18 patients showed deletions involving SMN exons 7 or 8, the most frequent gene alteration found in SMA. In addition, haplotype analysis in two large autosomal dominant pedigrees showed that the 5q13 locus was not segregating with the spinal CMT locus. Therefore, neither the sporadic nor the familial cases of spinal CMT are associated with a SMN gene deletion, nor are the familial cases linked to the 5q13 region, indicating that this neuropathy is genetically different from SMA.     

Qualité des supports de communication de crise lors de la pandémie de la COVID-19 au Grand Maghreb

ObjectiveTo objectively assess the quality of “crisis communication” media, during the COVID-19 pandemic, in the three Greater Maghreb countries (Tunisia, Algeria, Morocco).MethodsA compliance audit for press releases and epidemiological bulletins was analyzed against a quality benchmark, which had been specifically designed by the authors. This framework, made up of five dimensions and 50 items, graded (0/1), was applied by two researchers in preventive medicine. Multiplying the scores by a coefficient of two resulted in a partial score of 20 points for each dimension and a total score of 100 points for the checklist taken as a whole. The quality of the communication media was considered to be good when exceeding the thresholds of 15/20 for the different dimensions and 75/100 for the entire grid.ResultsA total of 141 information media were included in this audit (Tunisia: 60; Algeria: 60; Morocco: 21). The overall median quality score for these media was only 56/100 (IIQ: [46–58]), without major variability between countries. The most appreciated dimension was “maintaining the confidence of the population”, with an overall median score of 14/20 (12/20 for epidemiological bulletins and 16/20 for press releases). The most poorly rated dimension was “strengthening community participation”, with a median score of only 4/20 (6/20 for epidemiological bulletins and 4/20 for press releases).ConclusionThe quality of the Maghreb crisis communication media during COVID-19 was insufficient in most of its dimensions and items, particularly from a psychosocial standpoint. Reinforcement of the capacities of communication officers to develop information material and supports during health crises is indispensable and should be considered as an urgent matter.     

Familial lymphohistiocytosis. Evolution of management apropos of 3 cases

Familial lymphohistiocytosis is a rare rapidly lethal genetic disease. It is characterized by an uncontrolled activation of T lymphocytes and macrophages, with multiple organ infiltration, beginning with fever and unexplained coagulopathy. Recently, one of the genes implicated in 50% of families at risk was identified (locus FHL1, chromosome 10, region q21-22). Based on data suggesting an essential role of T lymphocytes in the genesis of familial lymphohistiocytosis, the treatment has recently evolved from a chemotherapy including Etoposide (VP16) and corticosteroids, sometimes efficient but toxic, to an almost always efficient and slightly toxic immunosuppressive treatment. These two treatments achieved a remission somewhat lasting with no definite cure. In fact, all patients relapsed in the central nervous system and died. Bone marrow transplantation (BMT) is the only curative treatment. However only 20% of patients benefit from an HLA identical BMT. Recent improvements in HLA non-identical BMT offer an acceptable alternative to the other 80% of patients. In this review, we present three cases illustrating the evolution and optimization in the management of infants with familial lymphohistiocytosis.     

EPIDEMIOLOGIE DE L’HYPERTENSION ARTERIELLE EN TUNISIE.Etude Hammam Sousse/Sahloul Heart Study (HSHS)

Introduction: Tunisia is experiencing a double burden of morbidity, characterized by the explosion of cardiovascular diseases and their risk factors including arterial Hypertension. The objective of this study, based on the HSHS cohort (Hammam Sousse Sahloul Heart Study), was to determine the prevalence of hypertension in the general population and to identify its predisposing factors. Methods: HSHS is a cardiovascular health promotion initiative in the city of Hammam Sousse (Tunisia). The study was conducted via a random sample of households, using the WHO PEV technique, made up of 33 clusters, of 33 households each. All people aged 20 and over, included, benefited from a questionnaire, a physical examination and a biological assessment. The Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) were measured from the average of the last two measurements, by an OMRON type tensiometer, of suitable width. These prevalences were adjusted according to sex and age group, by their weighting coefficients in the general population, and they were accompanied by their 95% CIs. Binary logistic regression was conducted to identify independent factors associated with hypertension. Results: The study population was composed of 481 men (33.4%) and 960 women (66.6%), with an average age of 49.6±16.35 years in males (M) and 46.6±16.18 in females (F). In addition to the family history of hypertension, the sufficient weekly consumption of vegetables and fruits was low (M: 32.4%, F: 24.9%). The adjusted rate of hypertension in the adult study population was 32.5%, 95%CI[31.9-33.1] (M: 36.4%, 95%CI[35, 5-37.3]; F: 28.4%; 95% CI[27.6-29.2]), reaching in the age group of 60 years and above: M: 74.6% (95%CI[66.9-82.3], F: 82.7% (95%CI[73.8-83.6]) Multivariate analysis identified five independent factors significantly associated with hypertension: male sex (ORa=1.55 [1.18-2.03]), age over 40 years (ORa=6.54[4.70-9.11]), low level of schooling (ORa=1.80 [1.36-2.38]), low physical activity (ORa=1.42[1.07-1.88]) and high socio-economic level (ORa=1 .84 [1.30-2.63]). Conclusion: The HSHS study confirmed the high prevalence of hypertension, and the extent of its low detection and control. Hence the need for a universal approach to health promotion, oriented towards the general population, piloted by its local organizations, based on the adoption of a healthy lifestyle, and centered on physical activity.