Diagnosis challenges in CHARGE syndrome: A novel variant and clinical description.

Introduction: In resource-limited settings, patients with uncommon phenotypes often face prolonged diagnostic journeys and potential misdiagnoses. Coloboma, heart defects, atresia choanae, restricted growth and development, genital and ear abnormalities syndrome (CHARGE) syndrome, a congenital condition affecting various body parts such as the heart, ears, eyes, and genitals, exemplifies this challenge. Case presentation: We present the case of a 21-year-old male patient from Ecuador who exhibited hypogonadism, facial deformities, and stunted growth. Due to the scarcity of genetic specialists and limited access to genetic testing in Ecuador, the patient received a misdiagnosis of Noonan syndrome. However, a correct diagnosis of CHARGE syndrome was ultimately reached after eight years, facilitated by genetic sequencing that identified a novel mutation in the Chromodomain helicase DNA binding protein 7 gene. Conclusion: This case highlights the critical role of meticulously assessing patients' symptoms and emphasizes the necessity for enhanced collaboration among physicians and researchers. Such efforts are pivotal in advancing healthcare access and equity for individuals in developing nations.

HLA allelic diversity in the Waorani population of Ecuador: Its significance to their ancestry and migration.

The Waorani, an isolated indigenous tribe in Ecuador, have long been characterized by limited genetic diversity, with few studies delving into their genetic background. Human Leukocyte Antigen (HLA) genes which are located in the human major histocompatibility complex (MHC) provides valuable insights into population evolution due to its highly polymorphic nature. However, little is known about the HLA diversity and ancestry of the Waorani population. In this study, we sequenced eight HLA genes using Next Generation Sequencing (NGS) from 134 Waorani individuals and obtained up to four-field HLA allele resolution. Cluster and phylogenetic analysis show that the Waorani are genetically distant from other Ecuador populations, but instead show genetic affinities with the Puyanawa and Terena tribes from Brazil, as well as the Mixe tribe from Mexico. The identification of alleles common within the Waorani population, previously linked to specific health conditions, notably paves the way for future association analyses. This extensive study, employing Next-Generation Sequencing (NGS) technology, significantly enriches the sparse and segmented understanding of HLA diversity in the South American region. Our findings enhance the global comprehension of human genetic diversity and underscore the value of studying indigenous populations. Such research is vital for deepening our insights into human migration patterns and evolutionary processes.

Risk HLA alleles in South America and potential new epitopes for SARS-CoV2.

HLA alleles are associated with the body's response to infection and the regulation of the immune system. HLA alleles have been reported to be involved in response to viral infections such as SARS-CoV2. Our study reviews the HLA alleles associated with protection or susceptibility to SARS-CoV2 and the prevalence of these HLA alleles in South America. Previous studies on HLA and SARS-CoV2 infection reported that HLA-A*02:02, HLA-B*15:03, and HLA-C*12:03 are protective; while HLA-A*25:01, HLA-B*46:01, and HLA-C*01:02 increase susceptibility. We identified that these alleles are not frequent in South America, confirmed that the spike protein is the most immunogenic protein of SARS-CoV2, and detected new immunogenic epitopes that bound to protective HLA alleles and to HLA alleles common in South America (binding score > 0.90). These could be used as vaccine targets.