Affiliations: [a] Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France
| [b] Muscle Research Unit, Experimental and Clinical Research Center, A Joint Cooperation between Max-Delbrück-Center for Molecular Medicine and Charite Medical Faculty, Berlin, Germany
Correspondence:
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Correspondence to: Anne T. Bertrand, Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, Institut de Myologie, Bâtiment Babinski, 47 Boulevard de l’Hôpital, 75651 Paris cedex 13, France. Tel.: +33 142165718; Fax: +33 142165700; E-mail: [email protected].
Note: [1] These authors contributed equally to the work.
Abstract: Background: Emery-Dreifuss muscular dystrophy (EDMD) is associated with mutations in EMD and LMNA genes, encoding for the nuclear envelope proteins emerin and lamin A/C, indicating that EDMD is a nuclear envelope disease. We recently reported mutations in FHL1 gene in X-linked EDMD. FHL1 encodes FHL1A, and the two minor isoforms FHL1B and FHL1C. So far, none have been described at the nuclear envelope. Objective: To gain insight into the pathophysiology of EDMD, we focused our attention on the poorly characterized FHL1B isoform. Methods: The amount and the localisation of FHL1B were evaluated in control and diseased human primary myoblasts using immunofluorescence and western blotting. Results: We found that in addition to a cytoplasmic localization, this isoform strongly accumulated at the nuclear envelope of primary human myoblasts, like but independently of lamin A/C and emerin. During myoblast differentiation, we observed a major reduction of FHL1B protein expression, especially in the nucleus. Interestingly, we found elevated FHL1B expression level in myoblasts from an FHL1-related EDMD patient where the FHL1 mutation only affects FHL1A, as well as in myoblasts from an LMNA-related EDMD patient. Conclusions: Altogether, the specific localization of FHL1B and its modulation in disease-patient’s myoblasts confirmed FHL1-related EDMD as a nuclear envelope disease.
