13q13.3 microdeletion associated with apparently balanced translocation of 46,XX,t(7;13) suggests NBEA involvement.

BACKGROUND: Deletion of 13q13.3 is an extremely rare event. CASE: We report on a 25-month-old girl with neurodevelopmental disorder and intellectual disability. She had dysmorphic facies characterized by synophrys, long and narrow palpebral fissures; and a large, round face with small organs such as the eyes and mouth positioned near the center. She was hypotonic and had autism-like behaviors. Blood tests and brain MRI revealed no specific findings. However, G-banding chromosome analysis showed an apparently balanced translocation: 46,XX,t(7,13)(q11.23;q12.3). Both parents had normal karyotypes. Furthermore, her abnormal phenotype and chromosomal breakpoint lesion were suspected to be associated. Hence, we conducted array comparative genomic hybridization, which revealed a 3.2 Mb novel pathological microdeletion at 13q13.3 involving 17 genes including neurobeachin (NBEA), a neurodevelopment disorder gene. Furthermore, fluorescence in situ hybridization using probes adjacent to the microdeletion suggested a concomitant occurrence of the deletion and translocation as the structural basis of this rare genomic variant. CONCLUSION: NBEA may have roles in her neurodevelopmental phenotypes, whereas other genes within the 13q13.3 microdeletion may contribute to her dysmorphic features.

Genome-wide Analysis of the Role of Copy Number Variation in Schizophrenia Risk in Chinese.

BACKGROUND: Compelling evidence suggested the role of copy number variations (CNVs) in schizophrenia susceptibility. Most of the evidence was from studies in populations with European ancestry. We tried to validate the associated CNV loci in a Han Chinese population and identify novel loci conferring risk of schizophrenia. METHODS: We performed a genome-wide CNV analysis on 6588 patients with schizophrenia and 11,904 control subjects of Han Chinese ancestry. RESULTS: Our data confirmed increased genome-wide CNV (>500 kb and <1%) burden in schizophrenia, and the increasing trend was more significant when only >1 Mb CNVs were considered. We also replicated several associated loci that were previously identified in European populations, including duplications at 16p11.2, 15q11.2-13.1, 7q11.23, and VIPR2 and deletions at 22q11.2, 1q21.1-q21.2, and NRXN1. In addition, we discovered three additional new potential loci (odds ratio >6, p < .05): duplications at 1p36.32, 10p12.1, and 13q13.3, involving many neurodevelopmental and synaptic related genes. CONCLUSIONS: Our findings provide further support for the role of CNVs in the etiology of schizophrenia.