There is currently an ongoing worldwide pandemic of a novel virus belonging to the family of Coronaviruses (CoVs) which are large, enveloped, plus-stranded RNA viruses. Coronaviruses belong to the order of Nidovirales, family of Coronavirinae and are divided into four genera: alphacoronavirus, betacoronavirus, gammacoronavirus and deltacoronavirus. CoVs cause diseases in a wide variety of birds and mammals and have been found in humans since 1960. To date, seven human CoVs were identified including the alpha-CoVs HCoVs-NL63 and HCoVs-229E and the beta-CoVs HCoVs-OC43, HCoVs-HKU1, the severe acute respiratory syndrome-CoV (SARS-CoV), the Middle East respiratory syndrome-CoV (MERS-CoV) and the novel virus that first appeared in December 2019 in Wuhan, China, and rapidly spread to 213 countries as of the writing this paper. It was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the international committee on taxonomy of viruses (ICTV) and the disease’s name is COVID-19 for coronavirus disease 2019. SARS-CoV-2 is very contagious and is capable of spreading from human to human. Infection routes include droplet and contact, and aerosol transmission is currently under investigation. It is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). SARS-CoV-2 became an emergency of international concern. As of July 12, 2020, the virus has been responsible for 12,698,995 confirmed cases and 564,924 deaths worldwide and the number is still increasing. Up until now, no specific treatment has yet been proven effective against SARS-CoV-2. Since the beginning of this outbreak, several interesting papers on SARS-CoV-2 and COVID-19 have been published to report on the phylogenetic evolution, epidemiology, pathogenesis, transmission as well as clinical characteristics of COVID-19 and possible treatments agents. This paper is a systematic review of the available literature on SARS-CoV-2. It was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and aims to help readers access the latest knowledge surrounding this new infectious disease and to provide a reference for future studies.

To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients.

Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

Epidermolysis bullosa simplex (EBS) is a skin disorder resulting from a weakened cytoskeleton of the proliferative compartment of the epidermis, leading to cell fragility and blistering. Although many mutations have been identified in intermediate filament keratins KRT5 and KRT14, detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. Therefore, we performed genomic and transcriptomic study in six Canadian EBS patients and six healthy subjects. We first characterized these patients at the genetic level and identified six pathogenic mutations of which two were novel. Then, we performed an expression microarray analysis of the EBS epidermis tissue to identify potential regulatory pathways altered in this disease. Expression profiling comparisons show that 28 genes are differentially expressed in EBS patients compared to control subjects and 41 genes in severe phenotype patients (EBS-DM) compared to their paired controls. Nine genes involved in fatty acid metabolism and two genes in epidermal keratinization are common altered expressed genes (up regulated) between the two subgroups. These two biological pathways contribute both to the formation of the cell envelope barrier and seem to be defective in the severe EBS phenotype. This study identifies, for the first time, the fatty acid metabolism disruption in EBS.

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DD skin displayed a constant immunohistochemical involucrin pattern characterized by both premature expression and a particular cytoplasmic/cell membrane localization distribution.

IntroductionMal 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 presentationA 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.ConclusionTo 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.

The Saguenay–Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes.We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders.