Relevance to Autism

Three de novo loss-of-function (LoF) variants in the DSCAM gene were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768), while a fourth de novo LoF variant in this gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Two additional de novo LoF variants were identified in Chinese ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329). Transmission and de novo association (TADA) analyses in Sanders et al., 2015 and Satterstrom et al., 2020 identified DSCAM as a candidate gene with a false discovery rate (FDR) 0.01. An intronic SNP in the DSCAM gene was found to associate with ASD in a GWAS meta-analysis of 7387 ASD cases and 8567 controls with a P-value < 1.0E-04 (Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium 2017). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified DSCAM as a gene reaching study-wide significance based on 5,754 constraint genes (P < 8.69E-06).

Molecular Function

This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD)

External Links

References