Combining Gene Mutation with Expression of Candidate Genes to Improve Diagnosis of Escobar Syndrome

Escobar syndrome is a rare, autosomal recessive disorder that affects the musculoskeletal system and the skin. Mutations in the CHRNG and TPM2 genes are associated with this pathology. In this study, we conducted a clinical and genetic investigation of five patients and also explored via in silico and gene expression analysis their phenotypic variability. In detail, we identified a patient with a novel composite heterozygous variant of the CHRNG gene and two recurrent mutations in both CHRNG and TPM2 in the rest of the patients. As for the clinical particularities, we reported a list of modifier genes in a patient suffering from myopathy. Moreover, we identified decreased expression of IGF-1, which could be related to the short stature of Escobar patients, and increased expression of POLG1 specific to patients with TPM2 mutation. Through this study, we identified the genetic spectrum of Escobar syndrome in the Tunisian population, which will allow setting up genetic counseling and prenatal diagnosis for families at risk. In addition, we highlighted relevant biomarkers that could differentiate between patients with different genetic defects

PIK3CA mutations in breast cancer: A Tunisian series.

BackgroundThe aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics.MethodsMutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed.ResultsFifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44%): 17/24 cases (71%) in exon 9, 5/24 cases (21%) in exon 20 and 2/24 cases (8%) in both exons. Of these 24 cases, 18 (75%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p > 0.05).ConclusionThe frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series

<i>PIK3CA</i> variant’s classification according to the American College of Medical Genetics and Genomics guidelines.

PIK3CA variant’s classification according to the American College of Medical Genetics and Genomics guidelines.</p

Prediction function and conservation of variants with unknown functions.

Prediction function and conservation of variants with unknown functions.</p

Association between PIK3CA mutations and clinicopathological characteristics of breast cancer.

Association between PIK3CA mutations and clinicopathological characteristics of breast cancer.</p

Fig 1 -

Electropherograms of the 15 PIK3CA variants identified in breast cancers (A) Known PIK3CA mutations (B) Novel variants. All sequences are in sense strand. Red rectangle box shows the position of the mutations. The major peak corresponds to the normal nucleotide and the minor peak corresponds to the mutant nucleotide. Altered nucleotide and amino acid positions and related codon substitution are shown of each corresponding sequence.</p

Distribution of mutation spectrum among breast cancer cases.

(A) Frequencies of the fifteen identified PIK3CA variants among breast cancer samples. (B) Proportion of samples with class 5 and 4 mutations. (C) Proportion of samples with concomitant or single mutations. (D) Proportion of samples with pathogenic class 5 and 4 PIK3CA mutations.</p

Summary of variants annotation using the reference sequence NM_006218.4 and classification according to ACMG.

Summary of variants annotation using the reference sequence NM_006218.4 and classification according to ACMG.</p

Primer sequences, annealing temperatures and product lengths.

Primer sequences, annealing temperatures and product lengths.</p

Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19

Documenting the circulation dynamics of SARS-CoV-2 variants in different regions of the world is crucial for monitoring virus transmission worldwide and contributing to global efforts towards combating the pandemic. Tunisia has experienced several waves of COVID-19 with a significant number of infections and deaths. The present study provides genetic information on the different lineages of SARS-CoV-2 that circulated in Tunisia over 17 months. Lineages were assigned for 1359 samples using whole-genome sequencing, partial S gene sequencing and variant-specific real-time RT-PCR tests. Forty-eight different lineages of SARS-CoV-2 were identified, including variants of concern (VOCs), variants of interest (VOIs) and variants under monitoring (VUMs), particularly Alpha, Beta, Delta, A.27, Zeta and Eta. The first wave, limited to imported and import-related cases, was characterized by a small number of positive samples and lineages. During the second wave, a large number of lineages were detected; the third wave was marked by the predominance of the Alpha VOC, and the fourth wave was characterized by the predominance of the Delta VOC. This study adds new genomic data to the global context of COVID-19, particularly from the North African region, and highlights the importance of the timely molecular characterization of circulating strains