Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Volume 155A, Issue 8, Pages 1865-1876Publisher
WILEY
DOI: 10.1002/ajmg.a.34081
Keywords
agenesis of the corpus callosum; schizophrenia; genetics; DISC1
Categories
Funding
- NIH/NCRR UCSF-CTSI [UL1 RR024131]
- NIHR (Manchester Biomedical Research Centre)
- NINDS [NS052192, NS058721]
- Wellcome Trust
Ask authors/readers for more resources
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. (C) Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available