In a recently published manuscript, we demonstrated the potential impact of complex and cryptic chromosomal abnormalities in children with early onset neuropsychiatric disorders. In this study, we find that the mainstay of genetic testing for prenatal and pediatric developmental anomalies of unknown etiology, clinical microarray to detect copy number variants (CNVs), is insufficient to detect a large number of genetic lesions that can contribute to disease. In follow-up analyses, we have now discovered that one class of complex rearrangement identified in this study, two duplications flanking a cryptic inversion, and other complex alterations, are remarkably common in the population, present in 12.4% of autism subjects sequenced, yet was never before identified by population based studies such as the 1,000 Genomes Project.
Brand H*, Pillalamarri V*, Collins R, Eggert S, O’Dushlaine C, Braaten EB, Stone M, Chambert K, Doty ND, Hanscom C, Rosenfeld JA, Ditmars H, Blais J, Mills R, Lee C, Gusella JF, McCarroll S, Smoller JW, Talkowski ME*, Doyle AE*. Cryptic and complex chromosomal aberrations in neuropsychiatric disorders. Am J Hum Genet. 2014 Oct 2;95(4):454-61.