Primary hypertriglyceridemia (PHTG) is characterized by a high concentration of triglycerides (TG); it is divided between familial hyperchylomicronemia syndrome and multifactorial chylomicronemia syndrome. In Mexico, hypertriglyceridemia constitutes a health problem in which the genetic bases have been scarcely explored; therefore, our objective was to describe biochemical–clinical characteristics and variants in the APOA5, GPIHBP1, LMF1, and LPL genes in patients with primary hypertriglyceridemia. Thirty DNA fragments were analyzed using PCR and Sanger sequencing in 58 unrelated patients. The patients’ main clinical–biochemical features were hypoalphalipoproteinemia (77.6%), pancreatitis (18.1%), and a TG median value of 773.9 mg/dL. A total of 74 variants were found (10 in APOA5, 16 in GPIHBP1, 34 in LMF1, and 14 in LPL), of which 15 could be involved in the development of PHTG: 3 common variants with significative odds and 12 heterozygous rare pathogenic variants distributed in 12 patients. We report on the first Mexican patient with hyperchylomicronemia syndrome due to GPIHBP1 deficiency caused by three variants: p.R145*, p.A154_G155insK, and p.A154Rfs*152. Moreover, eleven patients were heterozygous for the rare variants described as causing PHTG and also presented common variants of risk, which could partially explain their phenotype. In terms of findings, two novel genetic variants, c.-40_-22del LMF1 and p.G242Dfs*10 LPL, were identified.

Background/Objectives: Noonan syndrome (NS) is a genetic multisystem disease characterized by distinctive facial features, short stature, chest deformity, and congenital heart defects. NS is caused by gene variants of the RAS/MAPK pathway, with PTPN11 accounting for about 50% of cases. This study aimed to identify PTPN11 pathogenic variants in Mexican patients with NS to enhance our understanding of the disease in this population. Methods: This study included 91 probands and 60 relatives, all of which were clinically evaluated by a geneticist. Sanger sequencing was used to screen the entire PTPN11 gene. Results: Twenty-one previously reported pathogenic variants were identified in 47.3% of the probands. The most frequently occurring were p.Asn308Asp (16.3%) and p.Met504Val (16.3%). Variants p.Tyr279Cys and p.Thr468Met were found exclusively in patients with lentiginosis. Eighty-three percent of patients carried a variant in one of the three exons (3, 8, or 13) where the greatest genetic diversity was observed. Common clinical findings identified in probands included short stature (82%), cardiac anomalies (70.7%), short neck (68.4%), and pectus excavatum (63.2%), although features represented by only one patient each were also detected. Conclusions: This study confirmed the clinical diagnosis of NS in 43 probands and 11 relatives, and further genetic analysis of the remaining 48 probands is required to identify the causal variant. The genetic and clinical variability observed in our cohort was consistent with reports from other populations, underscoring the importance of comprehensive care for all patients. This research provides the most extensive clinical and molecular characterization of NS in Mexican patients, identifying pathogenic variants of PTPN11.

Genetic variants in the zone of polarizing activity regulatory sequence (ZRS) that induce ectopic expression of the SHH gene have been associated with different ZRS-related phenotypes. We report the first patient with a de novo variant, c.423+4916 T>C, in ZRS (previously classified as a variant of uncertain significance) that causes tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS). A two-month-old male patient presented with bilateral preaxial polydactyly, triphalangeal thumb, and tibial agenesis and was heterozygous for the variant c.423+4916T>C (neither of his parents was a carrier). The findings obtained from the family study were sufficient to reclassify the variant from “uncertain significance” to “likely pathogenic” according to three criteria from the American College of Medical Genetics and Genomics guidelines, as follows: (1) absence of gnomAD, (2) confirmation of paternity and maternity, and (3) strong phenotype–genotype association. In ZRS-associated syndromes, a wide clinical spectrum has been observed, ranging from polydactyly to THPTTS; our patient has the most severe and rare phenotype. We did not perform functional assays. However, the c.423+4916T>C variant is flanked by three variants, which have been proven not only to cause the phenotype but also to increase the expression of SHH. Through all this data gathering, we consider the c.423+4916T>C variant to be causative of THPTTS.

Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as “chemobrain,” is a frequent complication with a duration ranging from months to years, affecting between 17% and 70% of cancer patients. These cognitive deficits not only impair social, educational, and occupational functioning but may also impact survival outcomes, possibly by interfering with medication adherence and health-related behaviors. Emerging evidence has converged on an integrative cascade in which chemotherapy-induced systemic inflammation, intestinal dysbiosis, blood–brain barrier disruption, microglial/astroglial activation, and impaired hippocampal neurogenesis act in sequence rather than as independent pathways. Underlying pathophysiological mechanisms include neuroinflammation, reduced neurogenesis, loss of dendritic spines, oxidative stress, hormonal changes, epigenetic modifications, and mitochondrial dysfunction. In contrast, repair mechanisms involve complex glial responses, particularly those of astrocytes and microglia. Emerging studies suggest a link between changes in the microbiome and cognitive decline, demonstrating the importance of bidirectional communication in the gut–brain axis. Current research seeks to determine appropriate tests to identify chemobrain. Therefore, several biomarkers, such as GFAP, S100β, and isoprostanes, have been proposed to assess chemobrain, alongside screening tools such as MoCA, MMSE, and CAB-CF, to evaluate cognitive impairment and enable early detection. Pharmacological candidates—including lithium, fluoxetine, methylphenidate, modafinil, metformin, agomelatine, and melatonin—as well as nutritional and lifestyle interventions such as physical exercise, omega-3 fatty acids, curcumin, probiotics, and traditional Chinese medicine formulations—have been investigated, predominantly in animal models. These remain candidate, not validated, therapies; clinical evidence in CRCI populations is limited, heterogeneous, or absent, and well-powered randomized controlled trials are required before any recommendation can be issued. However, optimal strategies for symptom improvement remain unclear, as various approaches have yielded mixed outcomes. This review provides a comprehensive overview of chemobrain, focusing on its molecular mechanisms, interactions with the gut–brain axis, and potential therapeutic targets to improve the quality of life for cancer survivors.

Background: Griscelli syndrome type 2 is a rare autosomal recessive disorder caused by pathogenic variants in the RAB27A gene, characterized by partial albinism, immunodeficiency, and a high risk of hemophagocytic lymphohistiocytosis (HLH). Case descriptions: We report two unrelated Mexican patients with GS2 harboring the same homozygous RAB27A frameshift variant (c.335del; p.Asn112Thrfs*3) and describe their clinical and immunological features. Both patients presented with silvery-gray hair and subsequently developed HLH, although with variable onset and clinical course. One patient initially manifested with isolated central nervous system involvement, lacking systemic or laboratory abnormalities, which led to diagnostic uncertainty and delayed treatment. The second patient presented early in life with classical systemic features of HLH. Despite treatment with standard HLH-directed therapy, both patients experienced disease reactivation and ultimately died before undergoing hematopoietic stem cell transplantation. The homozygous pathogenic RAB27A variant (c.335del; p.Asn112Thrfs*3) was identified by polymerase chain reaction followed by Sanger sequencing in the two index cases; both sets of parents were heterozygous carriers. Comparison with previously reported cases carrying the same variant highlights notable phenotypic variability despite a shared genotype. The recurrence of this variant exclusively in individuals of Hispanic origin raises the possibility of a founder effect. Conclusions: These findings underscore the importance of early recognition of pigmentary abnormalities, the integration of clinical and molecular diagnostics approaches, and the consideration of HLH in patients presenting with atypical neurological manifestations. Early diagnosis is critical to enable prompt therapeutic intervention and improve clinical outcomes.