Mexican Patients With Suspected 22q11.2 Deletion Syndrome: Clinical Characterization and Molecular Findings by Fluorescence In Situ Hybridization and Multiplex Ligation‐Dependent Probe Amplification

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.