Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome
Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, s...
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| Veröffentlicht in: | American journal of medical genetics. Part A 2020-07, Vol.182 (7), p.1690-1696 |
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| container_title | American journal of medical genetics. Part A |
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| creator | Cucco, Francesco Sarogni, Patrizia Rossato, Sara Alpa, Mirella Patimo, Alessandra Latorre, Ana Magnani, Cinzia Puisac, Beatriz Ramos, Feliciano J. Pié, Juan Musio, Antonio |
| description | Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS‐like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery. |
| doi_str_mv | 10.1002/ajmg.a.61611 |
| format | Article |
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Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS‐like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery.</description><identifier>ISSN: 1552-4825</identifier><identifier>EISSN: 1552-4833</identifier><identifier>DOI: 10.1002/ajmg.a.61611</identifier><identifier>PMID: 32476269</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Abnormalities, Multiple - etiology ; Bone Diseases, Developmental - etiology ; Child ; Child, Preschool ; Chromatin remodeling ; Cohesin ; Cornelia de Lange syndrome ; De Lange syndrome ; De Lange Syndrome - etiology ; De Lange Syndrome - genetics ; E1A-Associated p300 Protein - genetics ; Facies ; Female ; Genetic diversity ; Genetic Variation ; Humans ; Infant ; Intellectual Disability - etiology ; KBG syndrome ; Male ; Phenotypes ; Repressor Proteins - genetics ; Rubinstein-Taybi Syndrome - etiology ; Rubinstein–Taybi syndrome ; Tooth Abnormalities - etiology ; Transcription ; Whole Exome Sequencing</subject><ispartof>American journal of medical genetics. Part A, 2020-07, Vol.182 (7), p.1690-1696</ispartof><rights>2020 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4451-15495171d505badc1a48e81fafc75b0382bf74efdf0413b6226e9348d3a223913</citedby><cites>FETCH-LOGICAL-c4451-15495171d505badc1a48e81fafc75b0382bf74efdf0413b6226e9348d3a223913</cites><orcidid>0000-0001-7701-6543</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajmg.a.61611$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajmg.a.61611$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32476269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cucco, Francesco</creatorcontrib><creatorcontrib>Sarogni, Patrizia</creatorcontrib><creatorcontrib>Rossato, Sara</creatorcontrib><creatorcontrib>Alpa, Mirella</creatorcontrib><creatorcontrib>Patimo, Alessandra</creatorcontrib><creatorcontrib>Latorre, Ana</creatorcontrib><creatorcontrib>Magnani, Cinzia</creatorcontrib><creatorcontrib>Puisac, Beatriz</creatorcontrib><creatorcontrib>Ramos, Feliciano J.</creatorcontrib><creatorcontrib>Pié, Juan</creatorcontrib><creatorcontrib>Musio, Antonio</creatorcontrib><title>Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome</title><title>American journal of medical genetics. Part A</title><addtitle>Am J Med Genet A</addtitle><description>Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS‐like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery.</description><subject>Abnormalities, Multiple - etiology</subject><subject>Bone Diseases, Developmental - etiology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromatin remodeling</subject><subject>Cohesin</subject><subject>Cornelia de Lange syndrome</subject><subject>De Lange syndrome</subject><subject>De Lange Syndrome - etiology</subject><subject>De Lange Syndrome - genetics</subject><subject>E1A-Associated p300 Protein - genetics</subject><subject>Facies</subject><subject>Female</subject><subject>Genetic diversity</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Infant</subject><subject>Intellectual Disability - etiology</subject><subject>KBG syndrome</subject><subject>Male</subject><subject>Phenotypes</subject><subject>Repressor Proteins - genetics</subject><subject>Rubinstein-Taybi Syndrome - etiology</subject><subject>Rubinstein–Taybi syndrome</subject><subject>Tooth Abnormalities - etiology</subject><subject>Transcription</subject><subject>Whole Exome Sequencing</subject><issn>1552-4825</issn><issn>1552-4833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90U1v00AQBuAVoqKlcOOMVuLCgYSd_bJ9jEIptAEqBOfV2B4nG-y12XVa5d_jkNIDh552tHr0ajQvY69AzEEI-R633XqOcwsW4Ak7A2PkTOdKPX2YpTllz1PaCqGEyewzdqqkzqy0xRn7dYPjpl9T8BW_xegxjIn7wC9ulBAcQ80XX6-_fwA4fA44ejqAOz9u-LCh0I_7gRLvbym2OAw-rPmyj4Faj7wmvsKwJp72oY59Ry_YSYNtopf37zn7-fHix_LTbPXt8vNysZpVWhuYgdGFgQxqI0yJdQWoc8qhwabKTClULssm09TUjdCgSiulpULpvFYopSpAnbO3x9wh9r93lEbX-VRR22Kgfpec1CI3KsszOdE3_9Ftv4th2m5SYISwxhaTendUVexTitS4IfoO496BcIcS3KEEh-5vCRN_fR-6KzuqH_C_q09AH8Gdb2n_aJhbXH25XBxz_wCDpJFi</recordid><startdate>202007</startdate><enddate>202007</enddate><creator>Cucco, Francesco</creator><creator>Sarogni, Patrizia</creator><creator>Rossato, Sara</creator><creator>Alpa, Mirella</creator><creator>Patimo, Alessandra</creator><creator>Latorre, Ana</creator><creator>Magnani, Cinzia</creator><creator>Puisac, Beatriz</creator><creator>Ramos, Feliciano J.</creator><creator>Pié, Juan</creator><creator>Musio, Antonio</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7701-6543</orcidid></search><sort><creationdate>202007</creationdate><title>Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome</title><author>Cucco, Francesco ; Sarogni, Patrizia ; Rossato, Sara ; Alpa, Mirella ; Patimo, Alessandra ; Latorre, Ana ; Magnani, Cinzia ; Puisac, Beatriz ; Ramos, Feliciano J. ; Pié, Juan ; Musio, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4451-15495171d505badc1a48e81fafc75b0382bf74efdf0413b6226e9348d3a223913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abnormalities, Multiple - etiology</topic><topic>Bone Diseases, Developmental - etiology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromatin remodeling</topic><topic>Cohesin</topic><topic>Cornelia de Lange syndrome</topic><topic>De Lange syndrome</topic><topic>De Lange Syndrome - etiology</topic><topic>De Lange Syndrome - genetics</topic><topic>E1A-Associated p300 Protein - genetics</topic><topic>Facies</topic><topic>Female</topic><topic>Genetic diversity</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Infant</topic><topic>Intellectual Disability - etiology</topic><topic>KBG syndrome</topic><topic>Male</topic><topic>Phenotypes</topic><topic>Repressor Proteins - genetics</topic><topic>Rubinstein-Taybi Syndrome - etiology</topic><topic>Rubinstein–Taybi syndrome</topic><topic>Tooth Abnormalities - etiology</topic><topic>Transcription</topic><topic>Whole Exome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cucco, Francesco</creatorcontrib><creatorcontrib>Sarogni, Patrizia</creatorcontrib><creatorcontrib>Rossato, Sara</creatorcontrib><creatorcontrib>Alpa, Mirella</creatorcontrib><creatorcontrib>Patimo, Alessandra</creatorcontrib><creatorcontrib>Latorre, Ana</creatorcontrib><creatorcontrib>Magnani, Cinzia</creatorcontrib><creatorcontrib>Puisac, Beatriz</creatorcontrib><creatorcontrib>Ramos, Feliciano J.</creatorcontrib><creatorcontrib>Pié, Juan</creatorcontrib><creatorcontrib>Musio, Antonio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of medical genetics. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cucco, Francesco</au><au>Sarogni, Patrizia</au><au>Rossato, Sara</au><au>Alpa, Mirella</au><au>Patimo, Alessandra</au><au>Latorre, Ana</au><au>Magnani, Cinzia</au><au>Puisac, Beatriz</au><au>Ramos, Feliciano J.</au><au>Pié, Juan</au><au>Musio, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome</atitle><jtitle>American journal of medical genetics. Part A</jtitle><addtitle>Am J Med Genet A</addtitle><date>2020-07</date><risdate>2020</risdate><volume>182</volume><issue>7</issue><spage>1690</spage><epage>1696</epage><pages>1690-1696</pages><issn>1552-4825</issn><eissn>1552-4833</eissn><abstract>Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS‐like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32476269</pmid><doi>10.1002/ajmg.a.61611</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-7701-6543</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Abnormalities, Multiple - etiology Bone Diseases, Developmental - etiology Child Child, Preschool Chromatin remodeling Cohesin Cornelia de Lange syndrome De Lange syndrome De Lange Syndrome - etiology De Lange Syndrome - genetics E1A-Associated p300 Protein - genetics Facies Female Genetic diversity Genetic Variation Humans Infant Intellectual Disability - etiology KBG syndrome Male Phenotypes Repressor Proteins - genetics Rubinstein-Taybi Syndrome - etiology Rubinstein–Taybi syndrome Tooth Abnormalities - etiology Transcription Whole Exome Sequencing |
| title | Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome |
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