Mosaicism in 22q11.2 Microdeletion Syndrome GC01-GC06
Dr. Ashutosh Halder,
Professor and Head, Department of Reproductive Biology, AIIMS, New Delhi-110029, India.
Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Fluorescence Polymerase Chain Reaction (QFPCR), array Comparative Genomic Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) microarray and Next-Generation Sequencing (NGS) techniques are commonly used for precise genetic diagnosis of microdeletion syndrome.
Aim: To study the role of mosaicism for the causation of phenotypic heterogeneity in 22q11.2 microdeletion syndrome.
Materials and Methods: In this study, for over the period of 10 years, we worked on detection of 22q11.2 microdeletion and observed mosaicism frequently. FISH analysis was used to assess level of mosaicism in metaphase and interphase cells derived from peripheral blood culture (lymphocytes) and interphase cells of various tissues like blood nucleated cells (mesodermal origin), buccal cells (ectodermal origin) and urinary exfoliated cells (endodermal origin). We have also used SNP microarray and QF PCR for further characterization.
Results: Among 257 cases of clinically suspected 22q11.2 microdeletion syndrome, presence of 22q11.2 microdeletion was confirmed in 39 cases (15.2%) by FISH. Eleven of 22q11.2 microdeletion cases (28.2%) were found to have mosaicism. We report high (28.2%) prevalence of mosaicism in 22q11.2 microdeletion syndrome and often (about 36% cases) low grade mosaicism (<35% deleted cells). Outsourced SNP microarray failed to detect low grade mosaicism. We also observed wide variations in deleted cell concentration amongst various tissues (blood, buccal and urinary cells).
Conclusion: We conclude that mosaicism in 22q11.2 microdeletion is common (28.2%) and interphase FISH should be the choice of test for detecting mosaicism.