Tetralogy of Fallot (ToF) is one of the most common and severe congenital heart defects (CHD). Recently, unbalanced structural genomic variants or copy number variations (CNVs) were proposed to be involved in the etiology of many complex diseases, including CHDs. The aim of this study was to investigate the frequency of CNVs in a region with a high density of CNVs, 22q11.2, and other regions with CHD-related genes in a sample of 52 Mexican mestizo patients with isolated ToF and negative fluorescence in situ hybridization staining for 22q11. CNVs were studied using two multiplex ligation-dependent probe amplification (MLPA) kits, SALSA P250-B1® (DiGeorge gene region) and SALSA MLPA P311-A1® CHD-related gene regions (GATA4, NKX2-5, TBX5, BMP4, and CRELD1). The MLPA assay detected a de novo CNV deletion of the probes located in exons 2 and 7 of the TBX1 gene in one of the 52 patients studied; this result was confirmed by real-time quantitative polymerase chain reaction. This deletion was not present in the patient's parents and 104 chromosomes from healthy control subjects. Our results clearly suggest a possible etiologic association between the TBX1 deletion and the ToF in our patient.

Background Myelomeningocele (MMC) is the most severe and frequent type of spina bifida. Its etiology remains poorly understood. The Hedgehog (Hh), Wnt, and planar cell polarity (PCP) signaling pathways are essential for normal tube closure, needing a structural‐functional cilium for its adequate function. The present study aimed to investigate the impact of different gene variants (GV) from those pathways on MMC genotype‐subphenotype correlations. Methods The study comprised 500 MMC trios and 500 controls, from 16 Telethon centers of 16 Mexican states. Thirty‐four GVs of 29 genes from cilia, Hh, PCP, and Wnt pathways, were analyzed, by an Illumina on design microarray. The total sample (T‐MMC) was stratified in High‐MMC (H‐MMC) when thoracic and Low‐MMC (L‐MMC) when lumbar‐sacral vertebrae affected. STATA/SE‐12.1 and PLINK software were used for allelic association, TDT, and gene–gene interaction (GGI) analyses, considering p value <.01 as statistically significant differences (SSD). Results Association analysis showed SSD for COBL‐rs10230120, DVL2‐rs2074216, PLCB4‐rs6077510 GVs in T‐MMC and L‐MMC, and VANGL2‐rs120886448 in T‐MMC and H‐MMC, and INVS‐rs7024375 exclusively in L‐MMC. TDT assay showed SSD preferential transmissions of C2CD3‐rs826058 in H‐MMC, and LRP5‐rs3736228, and BBS2‐rs1373 in L‐MMC. Statistically significant GGI was observed in four in T‐MMC, four completely different in L‐MMC, and one in H‐MMC. Interestingly, no one repeated in subphenotypes. Conclusions Our results support an association of GVs in Hh, Wnt, PCP, and cilia pathways, with MMC occurrence location, although further validation is needed. Furthermore, present results show a distinctive panel of gene‐variants in H‐MMC and LMMC subphenotypes, suggesting a feasible genotype–phenotype correlation.

The understanding of genetic and environmental determinants in the Mexican population is important for other Latin American populations as well, living in their own countries or moving to other ones, particular due to the current migration characteristics and particular genetic background like the Mexican Mestizo and other Central American populations with similar characteristics and migrating to neighbor developed countries, introducing their own smoking behavior and contributing importantly to the genetic pool of the receptor country.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objective: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, selfcompared after follow-up, and a reference group of sex-and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2,; p < 0.0001). Conclusion: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL. (REV INVEST CLIN. 2022;74(4):202-11