Introduction: Deletion 22q11.2 occurs in 1:4,000-1:6,000 live births while 10p13p14 deletion is found in 1:200,000 newborns. Both deletions have similar clinical features such as congenital heart disease and immunological anomalies. Objective: We looked for a 22q11.2 deletion in Mexican patients with craniofacial dysmorphisms suggestive of DiGeorge or velocardiofacial syndromes and at least one major phenotypic feature (cardiac anomaly, immune deficiency, palatal defects or development delay). Methods: A prospective study of 39 patients recruited in 2012-2015 at the Instituto Mexicano del Seguro Social at Guadalajara, Mexico. The patients with velocardiofacial syndrome-like features or a confirmed tetralogy of Fallot (TOF) or complex cardiopathy were studied by G-banding and fluorescence in situ hybridization (FISH) with a dual TUPLE1(HIRA)/ARSA or TUPLE1(22q11)/22q13(SHANK3) probe, six patients without the 22q11.2 deletion (arbitrarily selected) were tested with the dual DiGeorge II (10p14)/D10Z1 probe. Results: Twenty-two patients (7 males and 15 females) had the 22q11.2 deletion and 17/39 did not have it; no patient had a 10p loss. Among the 22 deleted patients, 19 had congenital heart disease (mostly TOF). Twelve patients without deletion had heart defects such as TOF (4/12), isolate ventricular septal defect (2/12) or other disorders (6/12). Conclusion: In our small sample about ~56% of the patients, regardless of the clinical diagnosis, had the expected 22q11.2 deletion. We remark the importance of early cytogenetic diagnosis in order to achieve a proper integral management of the patients and their families.

Background: The 22q11.2 deletion syndrome (22q11.2DS) is mostly caused by deletions of 3 and 1.5 Mb, referred to as typical deletions, although atypical deletions have also been reported. The commonest features are congenital heart disease, immunodeficiency, facial dysmorphism, and developmental delay. However, phenotypic variability is remarkable, and the underlying mechanisms remain poorly understood. Objective: To determine copy number variations (CNVs) in the 22q11.2 region and their association with clinical manifestations in Mexican patients with suspected 22q11.2DS. Methods: Fluorescence in situ Hybridization (FISH) and Multiplex Ligation‐dependent Probe Amplification (MLPA) assays were performed in 80 patients with suspected 22q11.2DS. Clinical characterization was carried out according to the criteria used by the 22q11.2 Consortium. Results: FISH detected deletions in 51%, while MLPA detected CNVs in 54%. Typical deletions were observed in 86% of patients, whereas atypical deletions were found in 14%, including CNVs involving single genes ( TBX1, TOP3B , and PRODH ). Three families were identified with the 3 Mb deletion and exhibited a heterogeneous phenotype that cannot be explained by the microdeletion alone. Conclusion: 22q11.2DS is a complex disorder for which MLPA is recommended to detect atypical deletions in FISH‐negative patients, and to define deletion size, breakpoints, and genes in FISH‐positive ones.

Introduction: Partial trisomy of the 6q24qter region is a rare chromosomal disorder characterized by variable clinical features and poorly understood mechanistic origins. Case Presentation: We describe a de novo complex der(6) chromosome in a patient with features consistent with partial 6q trisomy syndrome, including congenital heart disease, growth restriction, developmental delay, and dysmorphic traits. Molecular Findings: Whole-genome sequencing (WGS) identified duplications of 1.5 Mb on 6p25.3 and 23.3 Mb on 6q24.3–qter. While the 6p duplication appears benign, the phenotype is likely driven by dosage-sensitive 6q genes (ARID1B, TAB2, QKI) and possible additive effects from other duplicated genes. No parental pericentric inversion was detected by classical or molecular cytogenetics, and WGS revealed no inversion-associated breakpoints. Instead, chimeric (q−/q+) and truncated reads at the 6q junction support a replication-based origin, such as reversed template switching. FISH confirmed direct insertion of the 6q segment into 6p25.3, without a del/dup pattern typical of inversion-derived recombinants. Notably, WGS detected no direct 6p-6q junction reads but identified chimeric 6p-15q-6q reads with 2-bp microhomologies, suggesting that chromosome 15 transiently mediated the rearrangement. Interspersed telomeric sequences and flanking Alu elements were also found at both breakpoints. Conclusion: Altogether, these findings support a model in which replication fork stalling and template switching – potentially facilitated by telomere dynamics and repetitive elements – led to the formation of a recombinant-like der(6) chromosome. This case highlights the mechanistic complexity of structural rearrangements and the role of replication-based errors in shaping human genomic variation.