TY - JOUR
T1 - PTEN mutations in autism spectrum disorder and congenital hydrocephalus
T2 - developmental pleiotropy and therapeutic targets
AU - DeSpenza, Tyrone
AU - Carlson, Marina
AU - Panchagnula, Shreyas
AU - Robert, Stephanie
AU - Duy, Phan Q.
AU - Mermin-Bunnell, Nell
AU - Reeves, Benjamin C.
AU - Kundishora, Adam
AU - Elsamadicy, Aladine A.
AU - Smith, Hannah
AU - Ocken, Jack
AU - Alper, Seth L.
AU - Jin, Sheng Chih
AU - Hoffman, Ellen J.
AU - Kahle, Kristopher T.
N1 - Funding Information:
K.T.K. is supported by the National Institutes of Health (NRCDP K12 228168, 1RO1NS109358, and R01 NS111029-01A1); the Hydrocephalus Association, March of Dimes , Simons Foundation , Swebilius Foundation, and Rudi Schulte Research Institute . E.J.H. is supported by the National Institutes of Health (R01MH116002), Binational Science Foundation, Kavli Foundation , National Genetics Foundation, Simons Foundation , Spector Fund, and the Swebilius Foundation. T.D. is supported by the National Institutes of Health Medical Scientist Training Program Training Grant (T32GM007205) and National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number F31NS115519. M.C. is supported by the Interdepartmental Neuroscience Program at Yale and the National Institutes of Health Training Program Grant in Genetics NIH (5T32GM007499). The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/12
Y1 - 2021/12
N2 - The lack of effective treatments for autism spectrum disorder (ASD) and congenital hydrocephalus (CH) reflects the limited understanding of the biology underlying these common neurodevelopmental disorders. Although ASD and CH have been extensively studied as independent entities, recent human genomic and preclinical animal studies have uncovered shared molecular pathophysiology. Here, we review and discuss phenotypic, genomic, and molecular similarities between ASD and CH, and identify the PTEN–PI3K–mTOR (phosphatase and tensin homolog–phosphoinositide 3-kinase–mammalian target of rapamycin) pathway as a common underlying mechanism that holds diagnostic, prognostic, and therapeutic promise for individuals with ASD and CH.
AB - The lack of effective treatments for autism spectrum disorder (ASD) and congenital hydrocephalus (CH) reflects the limited understanding of the biology underlying these common neurodevelopmental disorders. Although ASD and CH have been extensively studied as independent entities, recent human genomic and preclinical animal studies have uncovered shared molecular pathophysiology. Here, we review and discuss phenotypic, genomic, and molecular similarities between ASD and CH, and identify the PTEN–PI3K–mTOR (phosphatase and tensin homolog–phosphoinositide 3-kinase–mammalian target of rapamycin) pathway as a common underlying mechanism that holds diagnostic, prognostic, and therapeutic promise for individuals with ASD and CH.
KW - mTOR
KW - macrocephaly
KW - neurodevelopmental disorders
KW - rapamycin
KW - ventriculomegaly
UR - http://www.scopus.com/inward/record.url?scp=85116570168&partnerID=8YFLogxK
U2 - 10.1016/j.tins.2021.08.007
DO - 10.1016/j.tins.2021.08.007
M3 - Review article
C2 - 34625286
AN - SCOPUS:85116570168
SN - 0166-2236
VL - 44
SP - 961
EP - 976
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 12
ER -