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Cited by 14Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersSchizophrenia research and treatment

Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage

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Woo, Young Jae, Kanellopoulos, Alexandros K., Hemati, Parisa, Kirschen, Jill, Nebel, Rebecca A., Wang, Tao, Bagni, Claudia, Abrahams, Brett S.·2019·Biological Psychiatry
DOI 10.1016/j.biopsych.2019.04.008PMC PMC6679746
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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.

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  • Among the four genes (TUBGCP5, CYFIP1, NIPA2, and NIPA1) in the 15q11.2 region, increasing evidence highlights the relevance of CYFIP1.

    “Among the four genes (TUBGCP5, CYFIP1, NIPA2, and NIPA1) encompassed within this narrow region, increasing evidence highlights the relevance of CYFIP1109.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [109]

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Authors
Woo, Y. J., Kanellopoulos, A. K., Hemati, P., Kirschen, J., Nebel, R. A., Wang, T., Bagni, C., & Abrahams, B. S.
Affiliations
  • Albert Einstein College of Medicine (US)
  • University of Lausanne (CH)
  • University of Rome Tor Vergata (IT)
Corresponding author
Abrahams, Brett S.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2019-08
Volume
86
Issue
4
Pages
306-314
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2019.04.008
PMC
PMC6679746
OpenAlex
W2939420829
Cited by
14
References
11
Citations by year
2025: 2 · 2024: 2 · 2023: 3 · 2021: 1 · 2020: 5 · 2019: 1
FWCI
1.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Lirias (submittedVersion, other-oa)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
  • National Center for Advancing Translational Sciences
  • National Center for Research Resources
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • National Institutes of Health
  • Autism Speaks
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
CYFIP1, cognitive impairment, working memory, arithmetic reasoning, grammatical reasoning, associative learning, non-associative learning, sensory perception, Drosophila, neurodevelopmental disorders, schizophrenia, epilepsy, Lumosity, online cognitive assessment
MeSH terms
Adult, Animals, Chromosome Aberrations, Chromosomes, Human, Pair 15, Drosophila, Female, Genotype, Humans, Male, Middle Aged, Phenotype, Cohort Studies, Drosophila Proteins, Adaptor Proteins, Signal Transducing, Cognitive Dysfunction, Neurodevelopmental Disorders

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