31 research outputs found
Genomics in neurodevelopmental disorders: an avenue to personalized medicine
Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental
disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in
genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous
mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered,
the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype-
based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in
genomic analysis and their translation into clinical practice
Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder
GWAS meta analysis identifies TSNARE1 as a novel Schizophrenia / Bipolar susceptibility locus
Accuracy and clinical value of maternal incidental findings during noninvasive prenatal testing for fetal aneuploidies
Accuracy and clinical value of maternal incidental findings during noninvasive prenatal testing for fetal aneuploidies
Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders
Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders
Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males