{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T18:07:04Z","timestamp":1772302024778,"version":"3.50.1"},"reference-count":27,"publisher":"EDP Sciences","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/www.edpsciences.org\/en\/authors\/copyright-and-licensing"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med Sci (Paris)"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:p>Les mutations du g\u00e8ne <jats:italic>FKRP<\/jats:italic> codant la fukutin-related protein (FKRP) sont \u00e0 l\u2019origine d\u2019un large \u00e9ventail de myopathies allant de formes s\u00e9v\u00e8res de dystrophies musculaires cong\u00e9nitales associ\u00e9es \u00e0 des anomalies structurales du syst\u00e8me nerveux central, jusqu\u2019\u00e0 des tableaux de myalgies \u00e0 l\u2019effort ou d\u2019hyperCK\u00e9mie asymptomatique, en passant par une forme de dystrophie musculaire des ceintures, la LGMD-R9 (ex-LGMD-2I), pour <jats:italic>limb girdle muscular dystrophy<\/jats:italic> r\u00e9cessive de type R9. La LGMD-R9 se caract\u00e9rise par un d\u00e9ficit proximal des ceintures pr\u00e9dominant initialement aux membres inf\u00e9rieurs, avec une atteinte respiratoire et cardiaque pouvant conditionner le pronostic vital. Le taux s\u00e9rique de CPK est nettement \u00e9lev\u00e9 et s\u2019accompagne, sur la biopsie musculaire, d\u2019une formule dystrophique associ\u00e9e \u00e0 une r\u00e9duction de la glycosylation de l\u2019\u03b1-dystroglycane visible en immunomarquage et par immunoblot. L\u2019IRM musculaire montre typiquement une atteinte des muscles proximaux (iliopsoas, adducteurs, grands fessiers, quadriceps) avec une relative pr\u00e9servation des muscles de la loge ant\u00e9rieure des cuisses (gracilis et sartorius). L\u2019analyse g\u00e9n\u00e9tique, par s\u00e9quen\u00e7age sp\u00e9cifique du g\u00e8ne <jats:italic>FKRP<\/jats:italic> ou d\u2019un panel regroupant l\u2019ensemble des g\u00e8nes impliqu\u00e9s dans la glycosylation de l\u2019\u03b1-dystroglycane, ou bien d\u2019un panel plus large de g\u00e8nes, confirme g\u00e9n\u00e9ralement le diagnostic, la mutation la plus fr\u00e9quente \u00e9tant le faux-sens p.(Leu276Ile). Actuellement, le traitement de la LGMD-R9 est symptomatique, requ\u00e9rant une approche pluridisciplinaire. Une \u00e9tude prospective d\u2019histoire naturelle de la maladie est en cours en Europe (GNT-015-FKRP). Des approches th\u00e9rapeutiques in\u00e9dites sont envisag\u00e9es, telles que la th\u00e9rapie g\u00e9nique m\u00e9di\u00e9e par des vecteurs d\u00e9riv\u00e9s du virus ad\u00e9no-associ\u00e9 (AAV). Celle-ci est efficace dans les mod\u00e8les animaux, permettant une correction des d\u00e9fauts de glycosylation de l\u2019a-dystroglycane et une augmentation de sa capacit\u00e9 de liaison \u00e0 la matrice extracellulaire. En parall\u00e8le, des \u00e9tudes pr\u00e9cliniques ont montr\u00e9, dans un mod\u00e8le animal, l\u2019efficacit\u00e9 du ribitol, un pentose alcool retrouv\u00e9 dans des compos\u00e9s naturels, ce qui a conduit \u00e0 un essai de phase I dont le d\u00e9veloppement clinique est en cours.<\/jats:p>","DOI":"10.1051\/medsci\/2020239","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T10:18:03Z","timestamp":1610360283000},"page":"28-33","source":"Crossref","is-referenced-by-count":7,"special_numbering":"Hors s\u00e9rie n\u00b0 2","title":["La dystrophie musculaire des ceintures de type R9 li\u00e9e au g\u00e8ne <i>FKRP<\/i>"],"prefix":"10.1051","volume":"36","author":[{"given":"Roc\u00edo Nur","family":"Villar Quiles","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Richard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Bouchet-Seraphin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"250","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1093\/hmg\/10.25.2851","volume":"10","author":"Brockington","year":"2001","journal-title":"Hum Mol Genet"},{"key":"R2","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1212\/01.WNL.0000058902.88181.3D","volume":"60","author":"Poppe","year":"2003","journal-title":"Neurology"},{"key":"R3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1056\/NEJMoa1006939","volume":"34464","author":"Hara","year":"2011","journal-title":"N Engl J Med"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Alhamidi M,\nKjeldsen Buvang E,\net al. 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