UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration
We report a 5‐generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67‐year‐old woman with amyotrophic lateral sclerosis. Disease onset...
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| Veröffentlicht in: | Annals of neurology 2014-05, Vol.75 (5), p.793-798 |
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| container_title | Annals of neurology |
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| creator | Fahed, Akl C. McDonough, Barbara Gouvion, Cynthia M. Newell, Kathy L. Dure, Leon S. Bebin, Martina Bick, Alexander G. Seidman, Jonathan G. Harter, Donald H. Seidman, Christine E. |
| description | We report a 5‐generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67‐year‐old woman with amyotrophic lateral sclerosis. Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin‐2 gene (UBQLN2) with X‐linked inheritance in all studied affected individuals. As ubiquilin‐2–positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations. ANN NEUROL 2014;75:793–798 |
| doi_str_mv | 10.1002/ana.24164 |
| format | Article |
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Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin‐2 gene (UBQLN2) with X‐linked inheritance in all studied affected individuals. As ubiquilin‐2–positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations. ANN NEUROL 2014;75:793–798</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.24164</identifier><identifier>PMID: 24771548</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adaptor Proteins, Signal Transducing ; Adolescent ; Adult ; Aged ; Autophagy-Related Proteins ; Cell Cycle Proteins - genetics ; Child, Preschool ; Female ; Genes, Dominant ; Genetic Heterogeneity ; Heredodegenerative Disorders, Nervous System - diagnosis ; Heredodegenerative Disorders, Nervous System - genetics ; Humans ; Male ; Mutation ; Mutation - genetics ; Neurodegeneration ; Pedigree ; Protein Folding ; Ubiquitins - genetics ; Young Adult</subject><ispartof>Annals of neurology, 2014-05, Vol.75 (5), p.793-798</ispartof><rights>2014 American Neurological Association</rights><rights>2014 American Neurological Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5804-57acafd404d0efb694b8e2a6e16e01e3120f5dca06431e8f60881e24f45a8c2d3</citedby><cites>FETCH-LOGICAL-c5804-57acafd404d0efb694b8e2a6e16e01e3120f5dca06431e8f60881e24f45a8c2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.24164$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.24164$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24771548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fahed, Akl C.</creatorcontrib><creatorcontrib>McDonough, Barbara</creatorcontrib><creatorcontrib>Gouvion, Cynthia M.</creatorcontrib><creatorcontrib>Newell, Kathy L.</creatorcontrib><creatorcontrib>Dure, Leon S.</creatorcontrib><creatorcontrib>Bebin, Martina</creatorcontrib><creatorcontrib>Bick, Alexander G.</creatorcontrib><creatorcontrib>Seidman, Jonathan G.</creatorcontrib><creatorcontrib>Harter, Donald H.</creatorcontrib><creatorcontrib>Seidman, Christine E.</creatorcontrib><title>UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>We report a 5‐generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67‐year‐old woman with amyotrophic lateral sclerosis. Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin‐2 gene (UBQLN2) with X‐linked inheritance in all studied affected individuals. As ubiquilin‐2–positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations. ANN NEUROL 2014;75:793–798</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Autophagy-Related Proteins</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Genes, Dominant</subject><subject>Genetic Heterogeneity</subject><subject>Heredodegenerative Disorders, Nervous System - diagnosis</subject><subject>Heredodegenerative Disorders, Nervous System - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neurodegeneration</subject><subject>Pedigree</subject><subject>Protein Folding</subject><subject>Ubiquitins - genetics</subject><subject>Young Adult</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhwB9AkbjAIe2Mv5JckJYK2qLV8lmBuFjeZLJ1m7WLnQD992R32xUgIXHywc_7aGZexh4jHCAAP7TeHnCJWt5hE1QC85LL6i6bgNAyVyjkHnuQ0gUAVBrhPtvjsihQyXLCTs9evp_NebYaetu74LPaDsn5ZXZOPcWwJE9hSNmXvHP-kpqsCSvnre8zT0MMDa2BuEk-ZPda2yV6dPPus7PXrz4dneSzt8enR9NZXqsSxnEKW9u2kSAboHahK7koiVtNqAmQBHJoVVNb0FIgla2GskTispXKljVvxD57sfVeDYsVNTX5PtrOXEW3svHaBOvMnz_enZtl-G4kguaqGgXPbgQxfBso9WblUk1dZze7mvEwwIUokP8HKmRRiQrW1qd_oRdhiH68xIbinKMqRur5lqpjSClSu5sbway7NGOXZtPlyD75fdEdeVveCBxugR-uo-t_m8x0Pr1V5tuESz393CVsvDS6EIUyn-fHhqsP7_Dk41fzRvwChE-3aw</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Fahed, Akl C.</creator><creator>McDonough, Barbara</creator><creator>Gouvion, Cynthia M.</creator><creator>Newell, Kathy L.</creator><creator>Dure, Leon S.</creator><creator>Bebin, Martina</creator><creator>Bick, Alexander G.</creator><creator>Seidman, Jonathan G.</creator><creator>Harter, Donald H.</creator><creator>Seidman, Christine E.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201405</creationdate><title>UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration</title><author>Fahed, Akl C. ; 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| subjects | Adaptor Proteins, Signal Transducing Adolescent Adult Aged Autophagy-Related Proteins Cell Cycle Proteins - genetics Child, Preschool Female Genes, Dominant Genetic Heterogeneity Heredodegenerative Disorders, Nervous System - diagnosis Heredodegenerative Disorders, Nervous System - genetics Humans Male Mutation Mutation - genetics Neurodegeneration Pedigree Protein Folding Ubiquitins - genetics Young Adult |
| title | UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration |
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