Related resources
Full-text held externally
- PMID: 21739582
- UKPMCID: 21739582
- DOI: 10.1002/ajmg.a.34081
Search for item elsewhere
University researcher(s)
Academic department(s)
Genetic and functional analyses identify DISC1 as a novel callosal agenesis candidate gene.
Osbun, Nathan; Li, Jiang; O'Driscoll, Mary C; Strominger, Zoe; Wakahiro, Mari; Rider, Eric; Bukshpun, Polina; Boland, Elena; Spurrell, Cailyn H; Schackwitz, Wendy; Pennacchio, Len A; Dobyns, William B; Black, Graeme C M; Sherr, Elliott H
American journal of medical genetics. Part A. 2011;155A(8):1865-76.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 21739582
- UKPMCID: 21739582
- DOI: 10.1002/ajmg.a.34081
Abstract
Agenesis of the corpus callosum (AgCC) is a congenital brain malformation that occurs in approximately 1:1,000-1:6,000 births. Several syndromes associated with AgCC have been traced to single gene mutations; however, the majority of AgCC causes remain unidentified. We investigated a mother and two children who all shared complete AgCC and a chromosomal deletion at 1q42. We fine mapped this deletion and show that it includes Disrupted-in-Schizophrenia 1 (DISC1), a gene implicated in schizophrenia and other psychiatric disorders. Furthermore, we report a de novo chromosomal deletion at 1q42.13 to q44, which includes DISC1, in another individual with AgCC. We resequenced DISC1 in a cohort of 144 well-characterized AgCC individuals and identified 20 sequence changes, of which 4 are rare potentially pathogenic variants. Two of these variants were undetected in 768 control chromosomes. One of these is a splice site mutation at the 5' boundary of exon 11 that dramatically reduces full-length mRNA expression of DISC1, but not of shorter forms. We investigated the developmental expression of mouse DISC1 and find that it is highly expressed in the embryonic corpus callosum at a critical time for callosal formation. Taken together our results suggest a significant role for DISC1 in corpus callosum development.