Detection of Chromosomal Breakpoints in Patients with Developmental Delay and Speech Disorders

摘要: Delineating candidate genes at the chromosomal breakpoint regions in apparently balanced chromosome rearrangements (ABCR) has been shown to be more effective with emergence of next-generation sequencing (NGS) technologies. We employed a large-insert (7–11 kb) paired-end tag technology (DNA-PET) systematically analyze genome four patients harbouring cytogenetically defined ABCR neurodevelopmental symptoms, including developmental delay (DD) and speech disorders. characterized structural variants (SVs) specific each individual, those matching breakpoints. Refinement these by Sanger resulted identification five disrupted three individuals: guanine nucleotide binding protein, q polypeptide (GNAQ), RNA-binding fox-1 homolog (RBFOX3), unc-5 D (C.elegans) (UNC5D), transmembrane protein 47 (TMEM47), X-linked inhibitor apoptosis (XIAP). Among them, XIAP is causative gene for immunodeficiency phenotype seen patient. The remaining displayed expression fetal brain have known biologically relevant functions development, suggesting putative phenotypes. This study demonstrates application NGS technologies mapping individual disruptions as resource deciphering human disorders (NDDs).