A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy

•Dolichol-P-mannose (DPM) synthase is essential for alpha-dystroglycan O-glycosylation.•DPM synthase is composed of 3 subunits (DPM1, DPM2, and DPM3).•DPM synthase mutations cause congenital muscular dystrophy with or without brain involvement.•Mutations in DPM3 can cause isolated, mild limb girdle...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Neuromuscular disorders : NMD 2017-11, Vol.27 (11), p.1043-1046
Hauptverfasser: Van den Bergh, P.Y.K., Sznajer, Y., Van Parys, V., van Tol, W., Wevers, R.A., Lefeber, D.J., Xu, L., Lek, M., MacArthur, D.G., Johnson, K., Phillips, L., Töpf, A., Straub, V.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1046
container_issue 11
container_start_page 1043
container_title Neuromuscular disorders : NMD
container_volume 27
creator Van den Bergh, P.Y.K.
Sznajer, Y.
Van Parys, V.
van Tol, W.
Wevers, R.A.
Lefeber, D.J.
Xu, L.
Lek, M.
MacArthur, D.G.
Johnson, K.
Phillips, L.
Töpf, A.
Straub, V.
description •Dolichol-P-mannose (DPM) synthase is essential for alpha-dystroglycan O-glycosylation.•DPM synthase is composed of 3 subunits (DPM1, DPM2, and DPM3).•DPM synthase mutations cause congenital muscular dystrophy with or without brain involvement.•Mutations in DPM3 can cause isolated, mild limb girdle muscular dystrophy. Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy.
doi_str_mv 10.1016/j.nmd.2017.07.006
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1928781317</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960896617304364</els_id><sourcerecordid>1928781317</sourcerecordid><originalsourceid>FETCH-LOGICAL-c353t-f3bd8131105b65132a468ab71f45a79ce63388746c55764ce76b9ff981203f953</originalsourceid><addsrcrecordid>eNp9kE1PAyEURYnR2Fr9AW4MSzdTYZgBJq6a-pnU6ELXhGGYlob5EBjN-Oulqbo0ecljcd4l9wBwjtEcI0yvtvO2qeYpwmyO4iB6AKaYM5KkhGaHYIoKihJeUDoBJ95vEcI5o-wYTFLOEeGYT0G9gJuu6b7GdTd4ePPyRGAzBBlM10LTQgn7-NZtgJ8mbKC0_UYm1eiD69Z2VLJNnLYy6Apa05RwbVxldUzwarDSwT3Zb8ZTcFRL6_XZz56Bt7vb1-VDsnq-f1wuVokiOQlJTcqKY4IxykuaY5LKjHJZMlxnuWSF0pQQzllGVR6bZEozWhZ1XXCcIlIXOZmBy31u77r3QfsgGuOVtla2OhYUuEg52_3AIor3qHKd907XonemkW4UGImdXrEVUa_Y6RUoDqLx5uInfigbXf1d_PqMwPUe0LHkh9FOeBX1KV0Zp1UQVWf-if8G6RyLHg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1928781317</pqid></control><display><type>article</type><title>A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Van den Bergh, P.Y.K. ; Sznajer, Y. ; Van Parys, V. ; van Tol, W. ; Wevers, R.A. ; Lefeber, D.J. ; Xu, L. ; Lek, M. ; MacArthur, D.G. ; Johnson, K. ; Phillips, L. ; Töpf, A. ; Straub, V.</creator><creatorcontrib>Van den Bergh, P.Y.K. ; Sznajer, Y. ; Van Parys, V. ; van Tol, W. ; Wevers, R.A. ; Lefeber, D.J. ; Xu, L. ; Lek, M. ; MacArthur, D.G. ; Johnson, K. ; Phillips, L. ; Töpf, A. ; Straub, V.</creatorcontrib><description>•Dolichol-P-mannose (DPM) synthase is essential for alpha-dystroglycan O-glycosylation.•DPM synthase is composed of 3 subunits (DPM1, DPM2, and DPM3).•DPM synthase mutations cause congenital muscular dystrophy with or without brain involvement.•Mutations in DPM3 can cause isolated, mild limb girdle muscular dystrophy. Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T &gt; G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy.</description><identifier>ISSN: 0960-8966</identifier><identifier>EISSN: 1873-2364</identifier><identifier>DOI: 10.1016/j.nmd.2017.07.006</identifier><identifier>PMID: 28803818</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Alpha-dystroglycan ; Dolichol-P-mannose synthase ; DPM3 ; Dystroglycans - metabolism ; Female ; Homozygote ; Humans ; Limb girdle muscular dystrophy ; Mannosyltransferases - genetics ; Membrane Proteins - genetics ; Middle Aged ; Muscle, Skeletal - diagnostic imaging ; Muscle, Skeletal - pathology ; Muscular Dystrophies, Limb-Girdle - diagnostic imaging ; Muscular Dystrophies, Limb-Girdle - genetics ; Muscular Dystrophies, Limb-Girdle - metabolism ; Muscular Dystrophies, Limb-Girdle - pathology ; Mutation ; Phenotype</subject><ispartof>Neuromuscular disorders : NMD, 2017-11, Vol.27 (11), p.1043-1046</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-f3bd8131105b65132a468ab71f45a79ce63388746c55764ce76b9ff981203f953</citedby><cites>FETCH-LOGICAL-c353t-f3bd8131105b65132a468ab71f45a79ce63388746c55764ce76b9ff981203f953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.nmd.2017.07.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28803818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van den Bergh, P.Y.K.</creatorcontrib><creatorcontrib>Sznajer, Y.</creatorcontrib><creatorcontrib>Van Parys, V.</creatorcontrib><creatorcontrib>van Tol, W.</creatorcontrib><creatorcontrib>Wevers, R.A.</creatorcontrib><creatorcontrib>Lefeber, D.J.</creatorcontrib><creatorcontrib>Xu, L.</creatorcontrib><creatorcontrib>Lek, M.</creatorcontrib><creatorcontrib>MacArthur, D.G.</creatorcontrib><creatorcontrib>Johnson, K.</creatorcontrib><creatorcontrib>Phillips, L.</creatorcontrib><creatorcontrib>Töpf, A.</creatorcontrib><creatorcontrib>Straub, V.</creatorcontrib><title>A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy</title><title>Neuromuscular disorders : NMD</title><addtitle>Neuromuscul Disord</addtitle><description>•Dolichol-P-mannose (DPM) synthase is essential for alpha-dystroglycan O-glycosylation.•DPM synthase is composed of 3 subunits (DPM1, DPM2, and DPM3).•DPM synthase mutations cause congenital muscular dystrophy with or without brain involvement.•Mutations in DPM3 can cause isolated, mild limb girdle muscular dystrophy. Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T &gt; G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy.</description><subject>Alpha-dystroglycan</subject><subject>Dolichol-P-mannose synthase</subject><subject>DPM3</subject><subject>Dystroglycans - metabolism</subject><subject>Female</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Limb girdle muscular dystrophy</subject><subject>Mannosyltransferases - genetics</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Muscle, Skeletal - diagnostic imaging</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Dystrophies, Limb-Girdle - diagnostic imaging</subject><subject>Muscular Dystrophies, Limb-Girdle - genetics</subject><subject>Muscular Dystrophies, Limb-Girdle - metabolism</subject><subject>Muscular Dystrophies, Limb-Girdle - pathology</subject><subject>Mutation</subject><subject>Phenotype</subject><issn>0960-8966</issn><issn>1873-2364</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PAyEURYnR2Fr9AW4MSzdTYZgBJq6a-pnU6ELXhGGYlob5EBjN-Oulqbo0ecljcd4l9wBwjtEcI0yvtvO2qeYpwmyO4iB6AKaYM5KkhGaHYIoKihJeUDoBJ95vEcI5o-wYTFLOEeGYT0G9gJuu6b7GdTd4ePPyRGAzBBlM10LTQgn7-NZtgJ8mbKC0_UYm1eiD69Z2VLJNnLYy6Apa05RwbVxldUzwarDSwT3Zb8ZTcFRL6_XZz56Bt7vb1-VDsnq-f1wuVokiOQlJTcqKY4IxykuaY5LKjHJZMlxnuWSF0pQQzllGVR6bZEozWhZ1XXCcIlIXOZmBy31u77r3QfsgGuOVtla2OhYUuEg52_3AIor3qHKd907XonemkW4UGImdXrEVUa_Y6RUoDqLx5uInfigbXf1d_PqMwPUe0LHkh9FOeBX1KV0Zp1UQVWf-if8G6RyLHg</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Van den Bergh, P.Y.K.</creator><creator>Sznajer, Y.</creator><creator>Van Parys, V.</creator><creator>van Tol, W.</creator><creator>Wevers, R.A.</creator><creator>Lefeber, D.J.</creator><creator>Xu, L.</creator><creator>Lek, M.</creator><creator>MacArthur, D.G.</creator><creator>Johnson, K.</creator><creator>Phillips, L.</creator><creator>Töpf, A.</creator><creator>Straub, V.</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>201711</creationdate><title>A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy</title><author>Van den Bergh, P.Y.K. ; Sznajer, Y. ; Van Parys, V. ; van Tol, W. ; Wevers, R.A. ; Lefeber, D.J. ; Xu, L. ; Lek, M. ; MacArthur, D.G. ; Johnson, K. ; Phillips, L. ; Töpf, A. ; Straub, V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-f3bd8131105b65132a468ab71f45a79ce63388746c55764ce76b9ff981203f953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alpha-dystroglycan</topic><topic>Dolichol-P-mannose synthase</topic><topic>DPM3</topic><topic>Dystroglycans - metabolism</topic><topic>Female</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Limb girdle muscular dystrophy</topic><topic>Mannosyltransferases - genetics</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Muscle, Skeletal - diagnostic imaging</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Dystrophies, Limb-Girdle - diagnostic imaging</topic><topic>Muscular Dystrophies, Limb-Girdle - genetics</topic><topic>Muscular Dystrophies, Limb-Girdle - metabolism</topic><topic>Muscular Dystrophies, Limb-Girdle - pathology</topic><topic>Mutation</topic><topic>Phenotype</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van den Bergh, P.Y.K.</creatorcontrib><creatorcontrib>Sznajer, Y.</creatorcontrib><creatorcontrib>Van Parys, V.</creatorcontrib><creatorcontrib>van Tol, W.</creatorcontrib><creatorcontrib>Wevers, R.A.</creatorcontrib><creatorcontrib>Lefeber, D.J.</creatorcontrib><creatorcontrib>Xu, L.</creatorcontrib><creatorcontrib>Lek, M.</creatorcontrib><creatorcontrib>MacArthur, D.G.</creatorcontrib><creatorcontrib>Johnson, K.</creatorcontrib><creatorcontrib>Phillips, L.</creatorcontrib><creatorcontrib>Töpf, A.</creatorcontrib><creatorcontrib>Straub, V.</creatorcontrib><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><jtitle>Neuromuscular disorders : NMD</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van den Bergh, P.Y.K.</au><au>Sznajer, Y.</au><au>Van Parys, V.</au><au>van Tol, W.</au><au>Wevers, R.A.</au><au>Lefeber, D.J.</au><au>Xu, L.</au><au>Lek, M.</au><au>MacArthur, D.G.</au><au>Johnson, K.</au><au>Phillips, L.</au><au>Töpf, A.</au><au>Straub, V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy</atitle><jtitle>Neuromuscular disorders : NMD</jtitle><addtitle>Neuromuscul Disord</addtitle><date>2017-11</date><risdate>2017</risdate><volume>27</volume><issue>11</issue><spage>1043</spage><epage>1046</epage><pages>1043-1046</pages><issn>0960-8966</issn><eissn>1873-2364</eissn><abstract>•Dolichol-P-mannose (DPM) synthase is essential for alpha-dystroglycan O-glycosylation.•DPM synthase is composed of 3 subunits (DPM1, DPM2, and DPM3).•DPM synthase mutations cause congenital muscular dystrophy with or without brain involvement.•Mutations in DPM3 can cause isolated, mild limb girdle muscular dystrophy. Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T &gt; G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>28803818</pmid><doi>10.1016/j.nmd.2017.07.006</doi><tpages>4</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0960-8966
ispartof Neuromuscular disorders : NMD, 2017-11, Vol.27 (11), p.1043-1046
issn 0960-8966
1873-2364
language eng
recordid cdi_proquest_miscellaneous_1928781317
source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Alpha-dystroglycan
Dolichol-P-mannose synthase
DPM3
Dystroglycans - metabolism
Female
Homozygote
Humans
Limb girdle muscular dystrophy
Mannosyltransferases - genetics
Membrane Proteins - genetics
Middle Aged
Muscle, Skeletal - diagnostic imaging
Muscle, Skeletal - pathology
Muscular Dystrophies, Limb-Girdle - diagnostic imaging
Muscular Dystrophies, Limb-Girdle - genetics
Muscular Dystrophies, Limb-Girdle - metabolism
Muscular Dystrophies, Limb-Girdle - pathology
Mutation
Phenotype
title A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T15%3A37%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20homozygous%20DPM3%20mutation%20in%20a%20patient%20with%20alpha-dystroglycan-related%20limb%20girdle%20muscular%20dystrophy&rft.jtitle=Neuromuscular%20disorders%20:%20NMD&rft.au=Van%20den%20Bergh,%20P.Y.K.&rft.date=2017-11&rft.volume=27&rft.issue=11&rft.spage=1043&rft.epage=1046&rft.pages=1043-1046&rft.issn=0960-8966&rft.eissn=1873-2364&rft_id=info:doi/10.1016/j.nmd.2017.07.006&rft_dat=%3Cproquest_cross%3E1928781317%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1928781317&rft_id=info:pmid/28803818&rft_els_id=S0960896617304364&rfr_iscdi=true