Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia.

Philadelphia Inquirer Features CAR's Virtual Reality Study
in Partnership with Philadelphia Police
Read more and learn how you can help!
 

TitleDeletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia.
Publication TypeJournal Article
Year of Publication2010
AuthorsMoreno-De-Luca, D, Mulle, JG, Kaminsky, EB, Sanders, SJ, Myers, SM, Adam, MP, Pakula, AT, Eisenhauer, NJ, Uhas, K, Weik, LA, Guy, L, Care, ME, Morel, CF, Boni, C, Salbert, BAnne, Chandrareddy, A, Demmer, LA, Chow, EWC, Surti, U, Aradhya, S, Pickering, DL, Golden, DM, Sanger, WG, Aston, E, Brothman, AR, Gliem, TJ, Thorland, EC, Ackley, T, Iyer, R, Huang, S, Barber, JC, Crolla, JA, Warren, ST, Martin, CL, Ledbetter, DH
Corporate AuthorsSGENE Consortium, Simons Simplex Collection Genetics Consortium, GeneSTAR
JournalAm J Hum Genet
Volume87
Issue5
Pagination618-30
Date Published2010 Nov 12
ISSN1537-6605
KeywordsChild, Child Development Disorders, Pervasive, Child, Preschool, Chromosomes, Human, Pair 17, DNA Copy Number Variations, Facies, Female, Humans, Male, Phenotype, Schizophrenia, Sequence Deletion
Abstract

Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10⁻⁵). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only.

DOI10.1016/j.ajhg.2010.10.004
Alternate JournalAm. J. Hum. Genet.
PubMed ID21055719
PubMed Central IDPMC2978962
Grant ListMH080129 / MH / NIMH NIH HHS / United States
R01 MH074090 / MH / NIMH NIH HHS / United States
MH081754 / MH / NIMH NIH HHS / United States
F32 MH080583 / MH / NIMH NIH HHS / United States
MH080583 / MH / NIMH NIH HHS / United States
HD064525 / HD / NICHD NIH HHS / United States
R01 MH071425 / MH / NIMH NIH HHS / United States
MH071425 / MH / NIMH NIH HHS / United States
RC2 HD064525 / HD / NICHD NIH HHS / United States
R01 MH080129 / MH / NIMH NIH HHS / United States
Comments
Leave a Comment