Deep phenotyping of an international series of patients with late‐onset dysferlinopathy
Background To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients. Methods Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International...
Gespeichert in:
| Veröffentlicht in: | European journal of neurology 2021-06, Vol.28 (6), p.2092-2102 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2102 |
|---|---|
| container_issue | 6 |
| container_start_page | 2092 |
| container_title | European journal of neurology |
| container_volume | 28 |
| creator | Fernández‐Eulate, Gorka Querin, Giorgia Moore, Ursula Behin, Anthony Masingue, Marion Bassez, Guillaume Leonard‐Louis, Sarah Laforêt, Pascal Maisonobe, Thierry Merle, Philippe‐Edouard Spinazzi, Marco Solé, Guilhem Kuntzer, Thierry Bedat‐Millet, Anne‐Laure Salort‐Campana, Emmanuelle Attarian, Shahram Péréon, Yann Feasson, Leonard Graveleau, Julie Nadaj‐Pakleza, Aleksandra Leturcq, France Gorokhova, Svetlana Krahn, Martin Eymard, Bruno Straub, Volker Evangelista, Teresinha Stojkovic, Tanya |
| description | Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy ( |
| doi_str_mv | 10.1111/ene.14821 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2527487858</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2501475026</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4221-17ffb5aaea68cd34e6a03b6749757e10ebadb745f5a4a2150acb247f4b6760993</originalsourceid><addsrcrecordid>eNqNkc9uEzEQxi1ERUvgwAuglbiA0LYe_1lvjlUIFCkqFzhwsrybWeLKsZe1l2pvPALPyJPgNCGVkCrhi0fj3zf-NB8hL4CeQz4X6PEcRM3gETkDUdUlcA6Pc80llBIonJKnMd5QSpli9Ak55VyBZJU8I1_fIfZFv0Ef0tRb_60IXWF8YX3CwZtkgzeuiDhYjLunPrfQp1jc2rQpnEn4--ev4COmYj3FDgdnfcjQZnpGTjrjIj4_3DPy5f3y8-KqXH368HFxuSpbwRiUoLqukcagqep2zQVWhvKmUmKupEKg2Jh1o4TspBGGgaSmbZhQnchMRedzPiNv9nM3xul-sFszTDoYq68uV3rXo5xVnAv4AZl9vWf7IXwfMSa9tbFF54zHMEbNJAWhJM2CGXn1D3oTxrwRt6OYErWqZX3_eTuEGAfsjg6A6l02Omej77LJ7MvDxLHZ4vpI_g0jA_UeuMUmdLHNi27xiOX0Ki6lAJErCgub7tJZhNGnLH37_9JMXxxo63B62LJeXi_33v8At8S5AQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2527487858</pqid></control><display><type>article</type><title>Deep phenotyping of an international series of patients with late‐onset dysferlinopathy</title><source>Wiley Online Library - AutoHoldings Journals</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Fernández‐Eulate, Gorka ; Querin, Giorgia ; Moore, Ursula ; Behin, Anthony ; Masingue, Marion ; Bassez, Guillaume ; Leonard‐Louis, Sarah ; Laforêt, Pascal ; Maisonobe, Thierry ; Merle, Philippe‐Edouard ; Spinazzi, Marco ; Solé, Guilhem ; Kuntzer, Thierry ; Bedat‐Millet, Anne‐Laure ; Salort‐Campana, Emmanuelle ; Attarian, Shahram ; Péréon, Yann ; Feasson, Leonard ; Graveleau, Julie ; Nadaj‐Pakleza, Aleksandra ; Leturcq, France ; Gorokhova, Svetlana ; Krahn, Martin ; Eymard, Bruno ; Straub, Volker ; Evangelista, Teresinha ; Stojkovic, Tanya</creator><creatorcontrib>Fernández‐Eulate, Gorka ; Querin, Giorgia ; Moore, Ursula ; Behin, Anthony ; Masingue, Marion ; Bassez, Guillaume ; Leonard‐Louis, Sarah ; Laforêt, Pascal ; Maisonobe, Thierry ; Merle, Philippe‐Edouard ; Spinazzi, Marco ; Solé, Guilhem ; Kuntzer, Thierry ; Bedat‐Millet, Anne‐Laure ; Salort‐Campana, Emmanuelle ; Attarian, Shahram ; Péréon, Yann ; Feasson, Leonard ; Graveleau, Julie ; Nadaj‐Pakleza, Aleksandra ; Leturcq, France ; Gorokhova, Svetlana ; Krahn, Martin ; Eymard, Bruno ; Straub, Volker ; Evangelista, Teresinha ; Stojkovic, Tanya ; Jain COS Consortium ; Jain COS Consortium</creatorcontrib><description>Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.
Results
Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.
Conclusions
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, including camptocormia, and are less severely affected compared with early‐onset patients. Furthermore, they present less necrosis and inflammation in muscle biopsy.</description><identifier>ISSN: 1351-5101</identifier><identifier>EISSN: 1468-1331</identifier><identifier>DOI: 10.1111/ene.14821</identifier><identifier>PMID: 33715265</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Biopsy ; Clinical Neurology ; Creatine ; Creatine kinase ; dysferlin ; Kinases ; late onset ; LGMDR2 ; Life Sciences ; Life Sciences & Biomedicine ; muscle pathology ; Muscles ; myopathy ; Necrosis ; Neurosciences ; Neurosciences & Neurology ; Phenotypes ; Phenotyping ; Regeneration ; Science & Technology ; Signs and symptoms</subject><ispartof>European journal of neurology, 2021-06, Vol.28 (6), p.2092-2102</ispartof><rights>2021 European Academy of Neurology</rights><rights>2021 European Academy of Neurology.</rights><rights>Copyright © 2021 European Academy of Neurology</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>10</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000635541400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c4221-17ffb5aaea68cd34e6a03b6749757e10ebadb745f5a4a2150acb247f4b6760993</citedby><cites>FETCH-LOGICAL-c4221-17ffb5aaea68cd34e6a03b6749757e10ebadb745f5a4a2150acb247f4b6760993</cites><orcidid>0000-0003-1112-7464 ; 0000-0002-4489-4718 ; 0000-0002-1846-3017 ; 0000-0002-4054-2838 ; 0000-0001-9046-3540 ; 0000-0001-9599-6573 ; 0000-0001-6870-4061 ; 0000-0002-8163-5539 ; 0000-0002-4602-2681 ; 0000-0002-9142-1382 ; 0000-0003-0048-9558</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fene.14821$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fene.14821$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,39263,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33715265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-03263341$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernández‐Eulate, Gorka</creatorcontrib><creatorcontrib>Querin, Giorgia</creatorcontrib><creatorcontrib>Moore, Ursula</creatorcontrib><creatorcontrib>Behin, Anthony</creatorcontrib><creatorcontrib>Masingue, Marion</creatorcontrib><creatorcontrib>Bassez, Guillaume</creatorcontrib><creatorcontrib>Leonard‐Louis, Sarah</creatorcontrib><creatorcontrib>Laforêt, Pascal</creatorcontrib><creatorcontrib>Maisonobe, Thierry</creatorcontrib><creatorcontrib>Merle, Philippe‐Edouard</creatorcontrib><creatorcontrib>Spinazzi, Marco</creatorcontrib><creatorcontrib>Solé, Guilhem</creatorcontrib><creatorcontrib>Kuntzer, Thierry</creatorcontrib><creatorcontrib>Bedat‐Millet, Anne‐Laure</creatorcontrib><creatorcontrib>Salort‐Campana, Emmanuelle</creatorcontrib><creatorcontrib>Attarian, Shahram</creatorcontrib><creatorcontrib>Péréon, Yann</creatorcontrib><creatorcontrib>Feasson, Leonard</creatorcontrib><creatorcontrib>Graveleau, Julie</creatorcontrib><creatorcontrib>Nadaj‐Pakleza, Aleksandra</creatorcontrib><creatorcontrib>Leturcq, France</creatorcontrib><creatorcontrib>Gorokhova, Svetlana</creatorcontrib><creatorcontrib>Krahn, Martin</creatorcontrib><creatorcontrib>Eymard, Bruno</creatorcontrib><creatorcontrib>Straub, Volker</creatorcontrib><creatorcontrib>Evangelista, Teresinha</creatorcontrib><creatorcontrib>Stojkovic, Tanya</creatorcontrib><creatorcontrib>Jain COS Consortium</creatorcontrib><creatorcontrib>Jain COS Consortium</creatorcontrib><title>Deep phenotyping of an international series of patients with late‐onset dysferlinopathy</title><title>European journal of neurology</title><addtitle>EUR J NEUROL</addtitle><addtitle>Eur J Neurol</addtitle><description>Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.
Results
Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.
Conclusions
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, including camptocormia, and are less severely affected compared with early‐onset patients. Furthermore, they present less necrosis and inflammation in muscle biopsy.</description><subject>Biopsy</subject><subject>Clinical Neurology</subject><subject>Creatine</subject><subject>Creatine kinase</subject><subject>dysferlin</subject><subject>Kinases</subject><subject>late onset</subject><subject>LGMDR2</subject><subject>Life Sciences</subject><subject>Life Sciences & Biomedicine</subject><subject>muscle pathology</subject><subject>Muscles</subject><subject>myopathy</subject><subject>Necrosis</subject><subject>Neurosciences</subject><subject>Neurosciences & Neurology</subject><subject>Phenotypes</subject><subject>Phenotyping</subject><subject>Regeneration</subject><subject>Science & Technology</subject><subject>Signs and symptoms</subject><issn>1351-5101</issn><issn>1468-1331</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><recordid>eNqNkc9uEzEQxi1ERUvgwAuglbiA0LYe_1lvjlUIFCkqFzhwsrybWeLKsZe1l2pvPALPyJPgNCGVkCrhi0fj3zf-NB8hL4CeQz4X6PEcRM3gETkDUdUlcA6Pc80llBIonJKnMd5QSpli9Ak55VyBZJU8I1_fIfZFv0Ef0tRb_60IXWF8YX3CwZtkgzeuiDhYjLunPrfQp1jc2rQpnEn4--ev4COmYj3FDgdnfcjQZnpGTjrjIj4_3DPy5f3y8-KqXH368HFxuSpbwRiUoLqukcagqep2zQVWhvKmUmKupEKg2Jh1o4TspBGGgaSmbZhQnchMRedzPiNv9nM3xul-sFszTDoYq68uV3rXo5xVnAv4AZl9vWf7IXwfMSa9tbFF54zHMEbNJAWhJM2CGXn1D3oTxrwRt6OYErWqZX3_eTuEGAfsjg6A6l02Omej77LJ7MvDxLHZ4vpI_g0jA_UeuMUmdLHNi27xiOX0Ki6lAJErCgub7tJZhNGnLH37_9JMXxxo63B62LJeXi_33v8At8S5AQ</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Fernández‐Eulate, Gorka</creator><creator>Querin, Giorgia</creator><creator>Moore, Ursula</creator><creator>Behin, Anthony</creator><creator>Masingue, Marion</creator><creator>Bassez, Guillaume</creator><creator>Leonard‐Louis, Sarah</creator><creator>Laforêt, Pascal</creator><creator>Maisonobe, Thierry</creator><creator>Merle, Philippe‐Edouard</creator><creator>Spinazzi, Marco</creator><creator>Solé, Guilhem</creator><creator>Kuntzer, Thierry</creator><creator>Bedat‐Millet, Anne‐Laure</creator><creator>Salort‐Campana, Emmanuelle</creator><creator>Attarian, Shahram</creator><creator>Péréon, Yann</creator><creator>Feasson, Leonard</creator><creator>Graveleau, Julie</creator><creator>Nadaj‐Pakleza, Aleksandra</creator><creator>Leturcq, France</creator><creator>Gorokhova, Svetlana</creator><creator>Krahn, Martin</creator><creator>Eymard, Bruno</creator><creator>Straub, Volker</creator><creator>Evangelista, Teresinha</creator><creator>Stojkovic, Tanya</creator><general>Wiley</general><general>John Wiley & Sons, Inc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</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>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-1112-7464</orcidid><orcidid>https://orcid.org/0000-0002-4489-4718</orcidid><orcidid>https://orcid.org/0000-0002-1846-3017</orcidid><orcidid>https://orcid.org/0000-0002-4054-2838</orcidid><orcidid>https://orcid.org/0000-0001-9046-3540</orcidid><orcidid>https://orcid.org/0000-0001-9599-6573</orcidid><orcidid>https://orcid.org/0000-0001-6870-4061</orcidid><orcidid>https://orcid.org/0000-0002-8163-5539</orcidid><orcidid>https://orcid.org/0000-0002-4602-2681</orcidid><orcidid>https://orcid.org/0000-0002-9142-1382</orcidid><orcidid>https://orcid.org/0000-0003-0048-9558</orcidid></search><sort><creationdate>202106</creationdate><title>Deep phenotyping of an international series of patients with late‐onset dysferlinopathy</title><author>Fernández‐Eulate, Gorka ; Querin, Giorgia ; Moore, Ursula ; Behin, Anthony ; Masingue, Marion ; Bassez, Guillaume ; Leonard‐Louis, Sarah ; Laforêt, Pascal ; Maisonobe, Thierry ; Merle, Philippe‐Edouard ; Spinazzi, Marco ; Solé, Guilhem ; Kuntzer, Thierry ; Bedat‐Millet, Anne‐Laure ; Salort‐Campana, Emmanuelle ; Attarian, Shahram ; Péréon, Yann ; Feasson, Leonard ; Graveleau, Julie ; Nadaj‐Pakleza, Aleksandra ; Leturcq, France ; Gorokhova, Svetlana ; Krahn, Martin ; Eymard, Bruno ; Straub, Volker ; Evangelista, Teresinha ; Stojkovic, Tanya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4221-17ffb5aaea68cd34e6a03b6749757e10ebadb745f5a4a2150acb247f4b6760993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biopsy</topic><topic>Clinical Neurology</topic><topic>Creatine</topic><topic>Creatine kinase</topic><topic>dysferlin</topic><topic>Kinases</topic><topic>late onset</topic><topic>LGMDR2</topic><topic>Life Sciences</topic><topic>Life Sciences & Biomedicine</topic><topic>muscle pathology</topic><topic>Muscles</topic><topic>myopathy</topic><topic>Necrosis</topic><topic>Neurosciences</topic><topic>Neurosciences & Neurology</topic><topic>Phenotypes</topic><topic>Phenotyping</topic><topic>Regeneration</topic><topic>Science & Technology</topic><topic>Signs and symptoms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernández‐Eulate, Gorka</creatorcontrib><creatorcontrib>Querin, Giorgia</creatorcontrib><creatorcontrib>Moore, Ursula</creatorcontrib><creatorcontrib>Behin, Anthony</creatorcontrib><creatorcontrib>Masingue, Marion</creatorcontrib><creatorcontrib>Bassez, Guillaume</creatorcontrib><creatorcontrib>Leonard‐Louis, Sarah</creatorcontrib><creatorcontrib>Laforêt, Pascal</creatorcontrib><creatorcontrib>Maisonobe, Thierry</creatorcontrib><creatorcontrib>Merle, Philippe‐Edouard</creatorcontrib><creatorcontrib>Spinazzi, Marco</creatorcontrib><creatorcontrib>Solé, Guilhem</creatorcontrib><creatorcontrib>Kuntzer, Thierry</creatorcontrib><creatorcontrib>Bedat‐Millet, Anne‐Laure</creatorcontrib><creatorcontrib>Salort‐Campana, Emmanuelle</creatorcontrib><creatorcontrib>Attarian, Shahram</creatorcontrib><creatorcontrib>Péréon, Yann</creatorcontrib><creatorcontrib>Feasson, Leonard</creatorcontrib><creatorcontrib>Graveleau, Julie</creatorcontrib><creatorcontrib>Nadaj‐Pakleza, Aleksandra</creatorcontrib><creatorcontrib>Leturcq, France</creatorcontrib><creatorcontrib>Gorokhova, Svetlana</creatorcontrib><creatorcontrib>Krahn, Martin</creatorcontrib><creatorcontrib>Eymard, Bruno</creatorcontrib><creatorcontrib>Straub, Volker</creatorcontrib><creatorcontrib>Evangelista, Teresinha</creatorcontrib><creatorcontrib>Stojkovic, Tanya</creatorcontrib><creatorcontrib>Jain COS Consortium</creatorcontrib><creatorcontrib>Jain COS Consortium</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>European journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernández‐Eulate, Gorka</au><au>Querin, Giorgia</au><au>Moore, Ursula</au><au>Behin, Anthony</au><au>Masingue, Marion</au><au>Bassez, Guillaume</au><au>Leonard‐Louis, Sarah</au><au>Laforêt, Pascal</au><au>Maisonobe, Thierry</au><au>Merle, Philippe‐Edouard</au><au>Spinazzi, Marco</au><au>Solé, Guilhem</au><au>Kuntzer, Thierry</au><au>Bedat‐Millet, Anne‐Laure</au><au>Salort‐Campana, Emmanuelle</au><au>Attarian, Shahram</au><au>Péréon, Yann</au><au>Feasson, Leonard</au><au>Graveleau, Julie</au><au>Nadaj‐Pakleza, Aleksandra</au><au>Leturcq, France</au><au>Gorokhova, Svetlana</au><au>Krahn, Martin</au><au>Eymard, Bruno</au><au>Straub, Volker</au><au>Evangelista, Teresinha</au><au>Stojkovic, Tanya</au><aucorp>Jain COS Consortium</aucorp><aucorp>Jain COS Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deep phenotyping of an international series of patients with late‐onset dysferlinopathy</atitle><jtitle>European journal of neurology</jtitle><stitle>EUR J NEUROL</stitle><addtitle>Eur J Neurol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>28</volume><issue>6</issue><spage>2092</spage><epage>2102</epage><pages>2092-2102</pages><issn>1351-5101</issn><eissn>1468-1331</eissn><abstract>Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.
Results
Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.
Conclusions
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, including camptocormia, and are less severely affected compared with early‐onset patients. Furthermore, they present less necrosis and inflammation in muscle biopsy.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>33715265</pmid><doi>10.1111/ene.14821</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1112-7464</orcidid><orcidid>https://orcid.org/0000-0002-4489-4718</orcidid><orcidid>https://orcid.org/0000-0002-1846-3017</orcidid><orcidid>https://orcid.org/0000-0002-4054-2838</orcidid><orcidid>https://orcid.org/0000-0001-9046-3540</orcidid><orcidid>https://orcid.org/0000-0001-9599-6573</orcidid><orcidid>https://orcid.org/0000-0001-6870-4061</orcidid><orcidid>https://orcid.org/0000-0002-8163-5539</orcidid><orcidid>https://orcid.org/0000-0002-4602-2681</orcidid><orcidid>https://orcid.org/0000-0002-9142-1382</orcidid><orcidid>https://orcid.org/0000-0003-0048-9558</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1351-5101 |
| ispartof | European journal of neurology, 2021-06, Vol.28 (6), p.2092-2102 |
| issn | 1351-5101 1468-1331 |
| language | eng |
| recordid | cdi_proquest_journals_2527487858 |
| source | Wiley Online Library - AutoHoldings Journals; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /> |
| subjects | Biopsy Clinical Neurology Creatine Creatine kinase dysferlin Kinases late onset LGMDR2 Life Sciences Life Sciences & Biomedicine muscle pathology Muscles myopathy Necrosis Neurosciences Neurosciences & Neurology Phenotypes Phenotyping Regeneration Science & Technology Signs and symptoms |
| title | Deep phenotyping of an international series of patients with late‐onset dysferlinopathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T09%3A23%3A39IST&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=Deep%20phenotyping%20of%20an%20international%20series%20of%20patients%20with%20late%E2%80%90onset%20dysferlinopathy&rft.jtitle=European%20journal%20of%20neurology&rft.au=Fern%C3%A1ndez%E2%80%90Eulate,%20Gorka&rft.aucorp=Jain%20COS%20Consortium&rft.date=2021-06&rft.volume=28&rft.issue=6&rft.spage=2092&rft.epage=2102&rft.pages=2092-2102&rft.issn=1351-5101&rft.eissn=1468-1331&rft_id=info:doi/10.1111/ene.14821&rft_dat=%3Cproquest_cross%3E2501475026%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=2527487858&rft_id=info:pmid/33715265&rfr_iscdi=true |