Identification of a DLG3 stop mutation in the MRX20 family
Here, we identified the causal mutation in the MRX20 family, one of the larger X-linked pedigrees that have been described in which no gene had been identified up till now. In 1995, the putative disease gene had been mapped to the pericentromeric region on the X chromosome, but no follow-up studies...
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| Veröffentlicht in: | European journal of human genetics : EJHG 2024-03, Vol.32 (3), p.317-323 |
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| creator | Huyghebaert, Jolien Mateiu, Ligia Elinck, Ellen Van Rossem, Kirsten Esther Christiaenssen, Bregje D'Incal, Claudio Peter McCormack, Michael K Lazzarini, Alice Vandeweyer, Geert Kooy, R Frank |
| description | Here, we identified the causal mutation in the MRX20 family, one of the larger X-linked pedigrees that have been described in which no gene had been identified up till now. In 1995, the putative disease gene had been mapped to the pericentromeric region on the X chromosome, but no follow-up studies were performed. Here, whole exome sequencing (WES) on two affected and one unaffected family member revealed the c.195del/p.(Thr66ProfsTer55) mutation in the DLG3 gene (NM_021120.4) that segregated with the affected individuals in the family. DLG3 mutations have been consequently associated with intellectual disability and are a plausible explanation for the clinical abnormalities observed in this family. In addition, we identified two other variants co-segregating with the phenotype: a stop gain mutation in SSX1 (c.358G>T/p.(Glu120Ter)) (NM_001278691.2) and a nonsynonymous SNV in USP27X (c.56 A>G/p.(Gln19Arg)) (NM_001145073.3). RNA sequencing revealed 14 differentially expressed genes (p value |
| doi_str_mv | 10.1038/s41431-024-01537-7 |
| format | Article |
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In 1995, the putative disease gene had been mapped to the pericentromeric region on the X chromosome, but no follow-up studies were performed. Here, whole exome sequencing (WES) on two affected and one unaffected family member revealed the c.195del/p.(Thr66ProfsTer55) mutation in the DLG3 gene (NM_021120.4) that segregated with the affected individuals in the family. DLG3 mutations have been consequently associated with intellectual disability and are a plausible explanation for the clinical abnormalities observed in this family. In addition, we identified two other variants co-segregating with the phenotype: a stop gain mutation in SSX1 (c.358G>T/p.(Glu120Ter)) (NM_001278691.2) and a nonsynonymous SNV in USP27X (c.56 A>G/p.(Gln19Arg)) (NM_001145073.3). RNA sequencing revealed 14 differentially expressed genes (p value < 0.1) in 7 affected males compared to 4 unaffected males of the family, including four genes known to be associated with neurological disorders. 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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-48521e96c136bd30f38255d049fc4e2bddb65355880c128865d0bb86cf027e63</citedby><cites>FETCH-LOGICAL-c375t-48521e96c136bd30f38255d049fc4e2bddb65355880c128865d0bb86cf027e63</cites><orcidid>0000-0003-1888-9066 ; 0009-0004-1507-8991 ; 0000-0003-2024-0485</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38273165$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huyghebaert, Jolien</creatorcontrib><creatorcontrib>Mateiu, Ligia</creatorcontrib><creatorcontrib>Elinck, Ellen</creatorcontrib><creatorcontrib>Van Rossem, Kirsten Esther</creatorcontrib><creatorcontrib>Christiaenssen, Bregje</creatorcontrib><creatorcontrib>D'Incal, Claudio Peter</creatorcontrib><creatorcontrib>McCormack, Michael K</creatorcontrib><creatorcontrib>Lazzarini, Alice</creatorcontrib><creatorcontrib>Vandeweyer, Geert</creatorcontrib><creatorcontrib>Kooy, R Frank</creatorcontrib><title>Identification of a DLG3 stop mutation in the MRX20 family</title><title>European journal of human genetics : EJHG</title><addtitle>Eur J Hum Genet</addtitle><description>Here, we identified the causal mutation in the MRX20 family, one of the larger X-linked pedigrees that have been described in which no gene had been identified up till now. 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Thus, in this paper we identified the c.195del/p.(Thr66ProfsTer55) mutation in the DLG3 gene (NM_021120.4) as likely responsible for the phenotype observed in the MRX20 family.</description><subject>Codon, Nonsense</subject><subject>Genes</subject><subject>Humans</subject><subject>Intellectual disabilities</subject><subject>Intellectual Disability - genetics</subject><subject>Male</subject><subject>Mental Retardation, X-Linked - genetics</subject><subject>Mutation</subject><subject>Neurological diseases</subject><subject>Nuclear Proteins - genetics</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Transcription Factors - genetics</subject><issn>1018-4813</issn><issn>1476-5438</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkD1PwzAQhi0EoqXwBxiQJRaWgO2zHYcNFSiVipBQBzYrcWyRKh8ldob-e1xSGPBi6-7xe6cHoUtKbikBdec55UATwnhCqIA0SY_QlPJUJoKDOo5vQlXCFYUJOvN-Q0hspvQUTUCxFKgUU3S_LG0bKleZPFRdizuHc_y4WgD2odviZghjvWpx-LT49f2DEezypqp35-jE5bW3F4d7htbPT-v5S7J6WyznD6vEQCpCnC8YtZk0FGRRAnFxuBAl4Zkz3LKiLAspQAiliKFMKRl7RaGkcYSlVsIM3Yyx2777GqwPuqm8sXWdt7YbvGYZy4hUEY7o9T900w19G5eLlGA8HsgixUbK9J33vXV621dN3u80JXovVo9idRSrf8TqffTVIXooGlv-ffk1Cd9372-N</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Huyghebaert, Jolien</creator><creator>Mateiu, Ligia</creator><creator>Elinck, Ellen</creator><creator>Van Rossem, Kirsten Esther</creator><creator>Christiaenssen, Bregje</creator><creator>D'Incal, Claudio Peter</creator><creator>McCormack, Michael K</creator><creator>Lazzarini, Alice</creator><creator>Vandeweyer, Geert</creator><creator>Kooy, R Frank</creator><general>Nature Publishing Group</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>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1888-9066</orcidid><orcidid>https://orcid.org/0009-0004-1507-8991</orcidid><orcidid>https://orcid.org/0000-0003-2024-0485</orcidid></search><sort><creationdate>20240301</creationdate><title>Identification of a DLG3 stop mutation in the MRX20 family</title><author>Huyghebaert, Jolien ; Mateiu, Ligia ; Elinck, Ellen ; Van Rossem, Kirsten Esther ; Christiaenssen, Bregje ; D'Incal, Claudio Peter ; McCormack, Michael K ; Lazzarini, Alice ; Vandeweyer, Geert ; Kooy, R Frank</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-48521e96c136bd30f38255d049fc4e2bddb65355880c128865d0bb86cf027e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Codon, Nonsense</topic><topic>Genes</topic><topic>Humans</topic><topic>Intellectual disabilities</topic><topic>Intellectual Disability - genetics</topic><topic>Male</topic><topic>Mental Retardation, X-Linked - genetics</topic><topic>Mutation</topic><topic>Neurological diseases</topic><topic>Nuclear Proteins - genetics</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huyghebaert, Jolien</creatorcontrib><creatorcontrib>Mateiu, Ligia</creatorcontrib><creatorcontrib>Elinck, Ellen</creatorcontrib><creatorcontrib>Van Rossem, Kirsten Esther</creatorcontrib><creatorcontrib>Christiaenssen, Bregje</creatorcontrib><creatorcontrib>D'Incal, Claudio Peter</creatorcontrib><creatorcontrib>McCormack, Michael K</creatorcontrib><creatorcontrib>Lazzarini, Alice</creatorcontrib><creatorcontrib>Vandeweyer, Geert</creatorcontrib><creatorcontrib>Kooy, R Frank</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>European journal of human genetics : EJHG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huyghebaert, Jolien</au><au>Mateiu, Ligia</au><au>Elinck, Ellen</au><au>Van Rossem, Kirsten Esther</au><au>Christiaenssen, Bregje</au><au>D'Incal, Claudio Peter</au><au>McCormack, Michael K</au><au>Lazzarini, Alice</au><au>Vandeweyer, Geert</au><au>Kooy, R Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a DLG3 stop mutation in the MRX20 family</atitle><jtitle>European journal of human genetics : EJHG</jtitle><addtitle>Eur J Hum Genet</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>32</volume><issue>3</issue><spage>317</spage><epage>323</epage><pages>317-323</pages><issn>1018-4813</issn><eissn>1476-5438</eissn><abstract>Here, we identified the causal mutation in the MRX20 family, one of the larger X-linked pedigrees that have been described in which no gene had been identified up till now. In 1995, the putative disease gene had been mapped to the pericentromeric region on the X chromosome, but no follow-up studies were performed. Here, whole exome sequencing (WES) on two affected and one unaffected family member revealed the c.195del/p.(Thr66ProfsTer55) mutation in the DLG3 gene (NM_021120.4) that segregated with the affected individuals in the family. DLG3 mutations have been consequently associated with intellectual disability and are a plausible explanation for the clinical abnormalities observed in this family. In addition, we identified two other variants co-segregating with the phenotype: a stop gain mutation in SSX1 (c.358G>T/p.(Glu120Ter)) (NM_001278691.2) and a nonsynonymous SNV in USP27X (c.56 A>G/p.(Gln19Arg)) (NM_001145073.3). RNA sequencing revealed 14 differentially expressed genes (p value < 0.1) in 7 affected males compared to 4 unaffected males of the family, including four genes known to be associated with neurological disorders. 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| subjects | Codon, Nonsense Genes Humans Intellectual disabilities Intellectual Disability - genetics Male Mental Retardation, X-Linked - genetics Mutation Neurological diseases Nuclear Proteins - genetics Pedigree Phenotype Phenotypes Transcription Factors - genetics |
| title | Identification of a DLG3 stop mutation in the MRX20 family |
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