María Isabel Mendoza-Ramos

Treacher Collins syndrome (TCS) is a rare disorder within the group of mandibulofacial dysostoses, occurring in 1 in 50,000 live births. It is characterized by anomalies in the maxillary, mandibular, and stapes bones, among others. TCS is caused by pathogenic variants in the TCOF1, POLR1D, POLR1C, and POLR1B genes with autosomal dominant or recessive inheritance patterns. Genetic data from Latin American populations remain scarce. Eleven patients from three different families were recruited. Whole-exome sequencing (WES) was performed on the probands to identify genetic variants, followed by Sanger sequencing for variant validation and familial segregation analysis. Finally, three-dimensional protein structures of wild-type and mutant proteins were predicted. In Family 1, a heterozygous pathogenic splice-site variant in the TCOF1 gene, c.4345 + 1 G > A, was identified and inherited from her mother. In Family 2, a heterozygous pathogenic variant in the TCOF1 gene, c.226_227insC (p.R77fs), was identified and inherited from the paternal lineage. In Family 3, a heterozygous pathogenic POLR1D variant, c.290_291delAG (p.G99fs), was identified among multiple affected relatives; direct parent-of-origin could not be established due to unavailability of one parent, but segregation supports autosomal dominant transmission across three generations. All findings were validated by Sanger sequencing. Our findings highlight the utility of WES for the molecular diagnosis of TCS and underscore the importance of including underrepresented populations in genetic studies to improve diagnosis, genetic counseling, and perinatal planning in at-risk pregnancies.

Flow cytometric immunophenotyping is essential for the diagnosis and immunologic classification of B-cell acute lymphoblastic leukemia in children and is traditionally performed using bone marrow aspirates, an invasive procedure that may be delayed or unavailable in certain clinical contexts. However, many patients present with circulating blasts at diagnosis, raising the possibility of using peripheral blood as an alternative source for initial immunophenotypic classification. Although previous studies have shown that peripheral blood can support initial diagnostic classification, they have not determined the degree of marker-level concordance between peripheral blood and bone marrow nor the clinical conditions under which this concordance is strongest. In this study, we evaluated the immunophenotypic concordance between peripheral blood and bone marrow in 32 pediatric patients with B-cell acute lymphoblastic leukemia, using paired samples obtained at diagnosis and analyzed with a standardized panel of B-lineage and maturation markers. Accordingly, the objective of this study was to quantify marker-specific agreement between compartments and identify clinical factors associated with higher concordance. Overall concordance was moderate across all subpopulations (mean CCC ~0.63) but higher for the markers most relevant to routine diagnostic classification (e.g., CD19⁺, CD10⁺, CD34⁺, and HLA-DR⁺), several of which exceeded 95% concordance and showed minimal bias between specimens. These findings apply only to newly diagnosed B-ALL with sufficient circulating blasts, as cases with minimal residual disease, low-blast presentations, atypical immunophenotypes, or mixed-lineage leukemias were not included in this study. The greatest concordance was seen in patients with hemoglobin < 8 g/dL, in whom extensive marrow infiltration promotes blast spillover into circulation. Likewise, patients older than 10 years showed high concordance, consistent with greater leukemic burden at presentation. Even in subgroups with lower circulating blast levels, such as those with hemoglobin ≥ 8 g/dL, peripheral blood adequately reproduced most leukemic cell populations present in bone marrow. Overall, these findings indicate that the markers and subpopulations most relevant for diagnostic immunophenotyping can be reliably assessed using peripheral blood in high-burden disease settings, reducing the immediate need for invasive procedures and facilitating timely immunophenotypic classification, particularly in resource-limited environments or situations where rapid initiation of treatment is critical.

Background/Objectives: B-cell acute lymphoblastic leukemia (B-ALL) presents a challenge in hematological malignancies due to its heterogeneity, which impacts treatment outcomes. Stratification based on the DNA index (DNAi) categorizes patients into favorable prognosis (hyperploid), standard prognosis (normoploid), and uncertain or poor prognosis (hypoploid) groups. In this study, we explored whether specific immunophenotypic markers are associated with each DNAi-based group and their potential connection to prognostic categories, aiming to provide new insights that may contribute to a better understanding of prognosis in B-ALL. Methods: In this study, we utilized flow cytometry to analyze immunophenotypic markers and combined this with DNA index (DNAi) measurements to stratify pediatric B-ALL patients into distinct risk categories. Our methodology focused on accurately classifying patients into hyperploid, normoploid, and hypoploid groups based on their DNA content, facilitating a comparative analysis of immunophenotypic characteristics across these groups. Results: Our analysis revealed that hypoploid B-ALL patients displayed a significantly lower percentage of cells in the S phase of the cell cycle compared to normoploid and hyperploid groups. Additionally, distinct immunophenotypic profiles were observed in hypoploid patients, characterized by higher expression levels of HLA-DR and a notable co-expression of CD34 and CD22. Conclusions: This study found that hypoploid B-ALL patients have distinct characteristics, such as lower S-phase cell percentages and specific immunophenotypic profiles, including higher HLA-DR expression and CD34/CD22 co-expression. These differences across DNA index-based prognostic categories warrant further research to explore their potential prognostic significance.

Background: Ellis–van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature, polydactyly, dystrophic nails, oral defects, and cardiac anomalies. It is caused by pathogenic variants in the EVC or EVC2 genes. To obtain further insight into the genetics of EvCS, we identified the genetic defect for the EVC2 gene in two Mexican patients. Methods: Two Mexican families were enrolled in this study. Exome sequencing was applied in the probands to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in the parents. Finally, a prediction of the three-dimensional structure of the mutant proteins was made. Results: One patient has a compound heterozygous EVC2 mutation: a novel heterozygous variant c.519_519 + 1delinsT inherited from her mother, and a heterozygous variant c.2161delC (p.L721fs) inherited from her father. The second patient has a previously reported compound heterozygous EVC2 mutation: nonsense mutation c.645G > A (p.W215*) in exon 5 inherited from her mother, and c.273dup (p.K92fs) in exon 2 inherited from her father. In both cases, the diagnostic was Ellis–van Creveld syndrome. Three-dimensional modeling of the EVC2 protein showed that truncated proteins are produced in both patients due to the generation of premature stop codons. Conclusion: The identified novel heterozygous EVC2 variants, c.2161delC and c.519_519 + 1delinsT, were responsible for the Ellis–van Creveld syndrome in one of the Mexican patients. In the second Mexican patient, we identified a compound heterozygous variant, c.645G > A and c.273dup, responsible for EvCS. The findings in this study extend the EVC2 mutation spectrum and may provide new insights into the EVC2 causation and diagnosis with implications for genetic counseling and clinical management.

Infections caused by micro-organisms of the genus Candida are becoming a growing health problem worldwide. These fungi are opportunistic commensals that can produce infections—clinically known as candidiasis—in immunocompromised individuals. The indiscriminate use of different anti-fungal treatments has triggered the resistance of Candida species to currently used therapies. In this sense, propolis has been shown to have potent antimicrobial properties and thus can be used as an approach for the inhibition of Candida species. Therefore, this work aims to evaluate the anti-Candida effects of a propolis extract obtained from the north of Mexico on clinical isolates of Candida species. Candida species were specifically identified from oral lesions, and both the qualitative and quantitative anti-Candida effects of the Mexican propolis were evaluated, as well as its inhibitory effect on C. albicans isolate’s germ tube growth and chemical composition. Three Candida species were identified, and our results indicated that the inhibition halos of the propolis ranged from 7.6 to 21.43 mm, while that of the MFC and FC₅₀ ranged from 0.312 to 1.25 and 0.014 to 0.244 mg/mL, respectively. Moreover, the propolis was found to inhibit germ tube formation (IC₅₀ ranging from 0.030 to 1.291 mg/mL). Chemical composition analysis indicated the presence of flavonoids, including pinocembrin, baicalein, pinobanksin chalcone, rhamnetin, and biochanin A, in the Mexican propolis extract. In summary, our work shows that Mexican propolis presents significant anti-Candida effects related to its chemical composition, and also inhibits germ tube growth. Other Candida species virulence factors should be investigated in future research in order to determine the mechanisms associated with antifungal effects against them.

The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient’s health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.

Infectious diseases are a significant problem affecting the public health and economic stability of societies all over the world. Treatment is available for most of these diseases; however, many pathogens have developed resistance to drugs, necessitating the development of new therapies with chemical agents, which can have serious side effects and high toxicity. In addition, the severity and aggressiveness of emerging and re-emerging diseases, such as pandemics caused by viral agents, have led to the priority of investigating new therapies to complement the treatment of different infectious diseases. Alternative and complementary medicine is widely used throughout the world due to its low cost and easy access and has been shown to provide a wide repertoire of options for the treatment of various conditions. In this work, we address the relevance of the effects of propolis on the causal pathogens of the main infectious diseases with medical relevance; the existing compiled information shows that propolis has effects on Gram-positive and Gram-negative bacteria, fungi, protozoan parasites and helminths, and viruses; however, challenges remain, such as the assessment of their effects in clinical studies for adequate and safe use.