Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes
AbstractBackgroundVariants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of oth...
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| Veröffentlicht in: | Biological psychiatry (1969) 2020-01, Vol.87 (2), p.123-131 |
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| creator | Beighley, Jennifer S Hudac, Caitlin M Arnett, Anne B Peterson, Jessica L Gerdts, Jennifer Wallace, Arianne S Mefford, Heather C Hoekzema, Kendra Turner, Tychele N O’Roak, Brian J Eichler, Evan E Bernier, Raphael A |
| description | AbstractBackgroundVariants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. MethodsThis study ( N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 ( CHD8 group) ( n = 15), 2) a gene targeted by CHD8 (target group) ( n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) ( n = 106). ResultsResults indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. ConclusionsThese similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations. |
| doi_str_mv | 10.1016/j.biopsych.2019.07.020 |
| format | Article |
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Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. MethodsThis study ( N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 ( CHD8 group) ( n = 15), 2) a gene targeted by CHD8 (target group) ( n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) ( n = 106). ResultsResults indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. ConclusionsThese similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2019.07.020</identifier><identifier>PMID: 31526516</identifier><language>eng</language><publisher>NEW YORK: Elsevier Inc</publisher><subject>Autism spectrum disorder ; Autism Spectrum Disorder - genetics ; CHD8 ; DNA-Binding Proteins - genetics ; Female ; Gene regulation ; Genetic subtypes ; Heterozygote ; Humans ; Life Sciences & Biomedicine ; Male ; Mutation ; Neurodevelopmental disorder ; Neurosciences ; Neurosciences & Neurology ; Phenotype ; Precision medicine ; Psychiatric/Mental Health ; Psychiatry ; Science & Technology ; Transcription Factors</subject><ispartof>Biological psychiatry (1969), 2020-01, Vol.87 (2), p.123-131</ispartof><rights>Society of Biological Psychiatry</rights><rights>2019 Society of Biological Psychiatry</rights><rights>Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>21</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000502949700008</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c526t-867bdd2265612b97cd6bcabead50f01a29825c2493e6c8cc8d50785c23a798643</citedby><cites>FETCH-LOGICAL-c526t-867bdd2265612b97cd6bcabead50f01a29825c2493e6c8cc8d50785c23a798643</cites><orcidid>0000-0001-8246-6477</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopsych.2019.07.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,28257,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31526516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beighley, Jennifer S</creatorcontrib><creatorcontrib>Hudac, Caitlin M</creatorcontrib><creatorcontrib>Arnett, Anne B</creatorcontrib><creatorcontrib>Peterson, Jessica L</creatorcontrib><creatorcontrib>Gerdts, Jennifer</creatorcontrib><creatorcontrib>Wallace, Arianne S</creatorcontrib><creatorcontrib>Mefford, Heather C</creatorcontrib><creatorcontrib>Hoekzema, Kendra</creatorcontrib><creatorcontrib>Turner, Tychele N</creatorcontrib><creatorcontrib>O’Roak, Brian J</creatorcontrib><creatorcontrib>Eichler, Evan E</creatorcontrib><creatorcontrib>Bernier, Raphael A</creatorcontrib><title>Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes</title><title>Biological psychiatry (1969)</title><addtitle>BIOL PSYCHIAT</addtitle><addtitle>Biol Psychiatry</addtitle><description>AbstractBackgroundVariants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. MethodsThis study ( N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 ( CHD8 group) ( n = 15), 2) a gene targeted by CHD8 (target group) ( n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) ( n = 106). ResultsResults indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. ConclusionsThese similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.</description><subject>Autism spectrum disorder</subject><subject>Autism Spectrum Disorder - genetics</subject><subject>CHD8</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Female</subject><subject>Gene regulation</subject><subject>Genetic subtypes</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Mutation</subject><subject>Neurodevelopmental disorder</subject><subject>Neurosciences</subject><subject>Neurosciences & Neurology</subject><subject>Phenotype</subject><subject>Precision medicine</subject><subject>Psychiatric/Mental Health</subject><subject>Psychiatry</subject><subject>Science & Technology</subject><subject>Transcription Factors</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkk1v1DAQhiMEotvCX6hyREIJ_kic5FKBArSVikBQzpbjTLpesvbWdhbtv-8s2a6AC5xsj993PvRMkpxTklNCxZtV3hm3CTu9zBmhTU6qnDDyJFnQuuIZKwh7miwIISLjjPGT5DSEFT4rxujz5ITTkomSikXytR2NNVqN6ZclWBd3GwipG9JWeW_A_7p_mqKKxtmQGpu2V-_r1Pn0Ooa0xRj4LfTprfJ3ENNLsBBeJM8GNQZ4eTjPku8fP9y2V9nN58vr9t1NprF4zGpRdX3PsA9BWddUuhedVh2oviQDoYo1NSs1KxoOQtda1xivaoxwVTW1KPhZcjHn3UzdGnoNNno1yo03a-V30ikj__yxZinv3FaKhpWccUzw6pDAu_sJQpRrEzSMo7LgpiAZa7CJAuUoFbNUexeCh-FYhhK5ByJX8hGI3AORpJIIBI3nvzd5tD0SQMHrWfATOjcEbcBqOMoQWUlYUzQV3kiN6vr_1a2ZubVushGtb2crIJMtspUHe2886Ch7Z_49zMVfKfRhe37ADsLKTd4icUllYJLIb_v9268fbXDcklf8Afvc1bE</recordid><startdate>20200115</startdate><enddate>20200115</enddate><creator>Beighley, Jennifer S</creator><creator>Hudac, Caitlin M</creator><creator>Arnett, Anne B</creator><creator>Peterson, Jessica L</creator><creator>Gerdts, Jennifer</creator><creator>Wallace, Arianne S</creator><creator>Mefford, Heather C</creator><creator>Hoekzema, Kendra</creator><creator>Turner, Tychele N</creator><creator>O’Roak, Brian J</creator><creator>Eichler, Evan E</creator><creator>Bernier, Raphael A</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8246-6477</orcidid></search><sort><creationdate>20200115</creationdate><title>Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes</title><author>Beighley, Jennifer S ; Hudac, Caitlin M ; Arnett, Anne B ; Peterson, Jessica L ; Gerdts, Jennifer ; Wallace, Arianne S ; Mefford, Heather C ; Hoekzema, Kendra ; Turner, Tychele N ; O’Roak, Brian J ; Eichler, Evan E ; Bernier, Raphael A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-867bdd2265612b97cd6bcabead50f01a29825c2493e6c8cc8d50785c23a798643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Autism spectrum disorder</topic><topic>Autism Spectrum Disorder - genetics</topic><topic>CHD8</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Female</topic><topic>Gene regulation</topic><topic>Genetic subtypes</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Mutation</topic><topic>Neurodevelopmental disorder</topic><topic>Neurosciences</topic><topic>Neurosciences & Neurology</topic><topic>Phenotype</topic><topic>Precision medicine</topic><topic>Psychiatric/Mental Health</topic><topic>Psychiatry</topic><topic>Science & Technology</topic><topic>Transcription Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beighley, Jennifer S</creatorcontrib><creatorcontrib>Hudac, Caitlin M</creatorcontrib><creatorcontrib>Arnett, Anne B</creatorcontrib><creatorcontrib>Peterson, Jessica L</creatorcontrib><creatorcontrib>Gerdts, Jennifer</creatorcontrib><creatorcontrib>Wallace, Arianne S</creatorcontrib><creatorcontrib>Mefford, Heather C</creatorcontrib><creatorcontrib>Hoekzema, Kendra</creatorcontrib><creatorcontrib>Turner, Tychele N</creatorcontrib><creatorcontrib>O’Roak, Brian J</creatorcontrib><creatorcontrib>Eichler, Evan E</creatorcontrib><creatorcontrib>Bernier, Raphael A</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beighley, Jennifer S</au><au>Hudac, Caitlin M</au><au>Arnett, Anne B</au><au>Peterson, Jessica L</au><au>Gerdts, Jennifer</au><au>Wallace, Arianne S</au><au>Mefford, Heather C</au><au>Hoekzema, Kendra</au><au>Turner, Tychele N</au><au>O’Roak, Brian J</au><au>Eichler, Evan E</au><au>Bernier, Raphael A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes</atitle><jtitle>Biological psychiatry (1969)</jtitle><stitle>BIOL PSYCHIAT</stitle><addtitle>Biol Psychiatry</addtitle><date>2020-01-15</date><risdate>2020</risdate><volume>87</volume><issue>2</issue><spage>123</spage><epage>131</epage><pages>123-131</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><abstract>AbstractBackgroundVariants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. MethodsThis study ( N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 ( CHD8 group) ( n = 15), 2) a gene targeted by CHD8 (target group) ( n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) ( n = 106). ResultsResults indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. ConclusionsThese similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.</abstract><cop>NEW YORK</cop><pub>Elsevier Inc</pub><pmid>31526516</pmid><doi>10.1016/j.biopsych.2019.07.020</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8246-6477</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Autism spectrum disorder Autism Spectrum Disorder - genetics CHD8 DNA-Binding Proteins - genetics Female Gene regulation Genetic subtypes Heterozygote Humans Life Sciences & Biomedicine Male Mutation Neurodevelopmental disorder Neurosciences Neurosciences & Neurology Phenotype Precision medicine Psychiatric/Mental Health Psychiatry Science & Technology Transcription Factors |
| title | Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes |
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