@article{d2e195c6ceb246b3b608f67032736e44,
title = "Delineation of a novel neurodevelopmental syndrome associated with PAX5 haploinsufficiency",
abstract = "PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues. Four of these individuals were published previously but without detailed clinical descriptions. All these individuals have been diagnosed with one or more neurodevelopmental phenotypes including delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. Seizures were documented in four individuals. No recurrent patterns of brain magnetic resonance imaging (MRI) findings, structural birth defects, or dysmorphic features were observed. Our findings suggest that PAX5 haploinsufficiency causes a neurodevelopmental disorder whose cardinal features include DD, variable ID, and/or ASD.",
author = "Yoel Gofin and Tianyun Wang and Gillentine, {Madelyn A.} and Scott, {Tiana M.} and Berry, {Aliska M.} and Azamian, {Mahshid S.} and Casie Genetti and Agrawal, {Pankaj B.} and Jonathan Picker and Wojcik, {Monica H.} and Delgado, {Mauricio R.} and Lynch, {Sally A.} and Scherer, {Stephen W.} and Howe, {Jennifer L.} and Bacino, {Carlos A.} and Stephanie DiTroia and VanNoy, {Grace E.} and Anne O'Donnell-Luria and Lalani, {Seema R.} and Graf, {William D.} and Rosenfeld, {Jill A.} and Eichler, {Evan E.} and Earl, {Rachel K.} and Scott, {Daryl A.}",
note = "Funding Information: We would like to thank Andres Hernandez-Garcia and Paula Patricia Hernandez for their help in DNA extraction and sample handling.?This study makes use of data generated by the DECIPHER community. A full list of centers that contributed to the generation of the data is available at https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by Wellcome (https://wellcome.org/). Subjects were also accrued with the help of GeneMatcher (Sobreira et al.,?2015), denovo-db (https://denovo-db.gs.washington.edu/denovo-db/), Simons Powering Autism Research (SPARK, https://sparkforautism.org/), Baylor Genetics (https://www.baylorgenetics.com/), and Matchmaker Exchange (https://www.matchmakerexchange.org/).?The authors wish to acknowledge the use of resources from Autism Speaks, The Centre for Applied Genomics at The Hospital for Sick Children, Toronto, Canada, and the help of the Simons Foundation Powering Autism Research (SPARK) Consortium (Supporting Information). We also thank the participating families for their time and contributions to this database, as well as the generosity of the donors who supported this program.?Sequencing and analysis for Subjects 13 and 14 were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and, in part, by National Human Genome Research Institute grants R01 HG009141 and U01 HG011755. Sequencing for Subject 14 was also supported by Chan Zuckerberg Initiative DAF grant 2020-224274, and by an advised fund of the Silicon Valley Community Foundation. M. H. W. is supported by K23 HD102589.?This study was also supported, in part, by grants to E. E. E. from the National Institutes of Health, R01 MH101221, and the Simons Foundation, SFARI 608045. E. E. E. is an investigator of the Howard Hughes Medical Institute. Funding Information: We would like to thank Andres Hernandez‐Garcia and Paula Patricia Hernandez for their help in DNA extraction and sample handling. This study makes use of data generated by the DECIPHER community. A full list of centers that contributed to the generation of the data is available at https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org . Funding for the DECIPHER project was provided by Wellcome ( https://wellcome.org/ ). Subjects were also accrued with the help of GeneMatcher (Sobreira et al., 2015 ), denovo‐db ( https://denovo-db.gs.washington.edu/denovo-db/ ), Simons Powering Autism Research (SPARK, https://sparkforautism.org/ ), Baylor Genetics ( https://www.baylorgenetics.com/ ), and Matchmaker Exchange ( https://www.matchmakerexchange.org/ ). The authors wish to acknowledge the use of resources from Autism Speaks, The Centre for Applied Genomics at The Hospital for Sick Children, Toronto, Canada, and the help of the Simons Foundation Powering Autism Research (SPARK) Consortium (Supporting Information). We also thank the participating families for their time and contributions to this database, as well as the generosity of the donors who supported this program. Sequencing and analysis for Subjects 13 and 14 were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and, in part, by National Human Genome Research Institute grants R01 HG009141 and U01 HG011755. Sequencing for Subject 14 was also supported by Chan Zuckerberg Initiative DAF grant 2020‐224274, and by an advised fund of the Silicon Valley Community Foundation. M. H. W. is supported by K23 HD102589. This study was also supported, in part, by grants to E. E. E. from the National Institutes of Health, R01 MH101221, and the Simons Foundation, SFARI 608045. E. E. E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",
year = "2022",
doi = "10.1002/humu.24332",
language = "English (US)",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
}