Young Jae Woo1, Alexandros K Kanellopoulos2, Parisa Hemati3, Jill Kirschen4, Rebecca A Nebel5, Tao Wang6, Claudia Bagni7, Brett S Abrahams8. 1. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. 2. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland. 3. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York; Human Genetics Program, Sarah Lawrence College, Yonkers, New York. 4. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York. 5. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York. 6. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 7. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. 8. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York. Electronic address: brett.abrahams@einstein.yu.edu.
Abstract
BACKGROUND: Deletions encompassing a four-gene region on chromosome 15 (BP1-BP2 at 15q11.2), seen at a population frequency of 1 in 500, are associated with increased risk for schizophrenia, epilepsy, and other common neurodevelopmental disorders. However, little is known in terms of how these common deletions impact cognition. METHODS: We used a Web-based tool to characterize cognitive function in a novel cohort of adult carriers and their noncarrier family members. Results from 31 carrier and 38 noncarrier parents from 40 families were compared with control data from 6530 individuals who self-registered on the Lumosity platform and opted in to participate in research. We then examined aspects of sensory and cognitive function in flies harboring a mutation in Cyfip, the homologue of one of the genes within the deletion. For the fly studies, 10 or more groups of 50 individuals per genotype were included. RESULTS: Our human studies revealed profound deficits in grammatical reasoning, arithmetic reasoning, and working memory in BP1-BP2 deletion carriers. No such deficits were observed in noncarrier spouses. Our fly studies revealed deficits in associative and nonassociative learning despite intact sensory perception. CONCLUSIONS: Our results provide new insights into outcomes associated with BP1-BP2 deletions and call for a discussion on how to appropriately communicate these findings to unaffected carriers. Findings also highlight the utility of an online tool in characterizing cognitive function in a geographically distributed population.
BACKGROUND: Deletions encompassing a four-gene region on chromosome 15 (BP1-BP2 at 15q11.2), seen at a population frequency of 1 in 500, are associated with increased risk for schizophrenia, epilepsy, and other common neurodevelopmental disorders. However, little is known in terms of how these common deletions impact cognition. METHODS: We used a Web-based tool to characterize cognitive function in a novel cohort of adult carriers and their noncarrier family members. Results from 31 carrier and 38 noncarrier parents from 40 families were compared with control data from 6530 individuals who self-registered on the Lumosity platform and opted in to participate in research. We then examined aspects of sensory and cognitive function in flies harboring a mutation in Cyfip, the homologue of one of the genes within the deletion. For the fly studies, 10 or more groups of 50 individuals per genotype were included. RESULTS: Our human studies revealed profound deficits in grammatical reasoning, arithmetic reasoning, and working memory in BP1-BP2 deletion carriers. No such deficits were observed in noncarrier spouses. Our fly studies revealed deficits in associative and nonassociative learning despite intact sensory perception. CONCLUSIONS: Our results provide new insights into outcomes associated with BP1-BP2 deletions and call for a discussion on how to appropriately communicate these findings to unaffected carriers. Findings also highlight the utility of an online tool in characterizing cognitive function in a geographically distributed population.
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