Abstract
Autosomal dominant limb girdle muscular dystrophy D3 HNRNPDL-related is a rare dominant myopathy caused by mutations in HNRNPDL. Only three unrelated families have been described worldwide, a Brazilian and a Chinese carrying the mutation c.1132G>A p.(Asp378Asn), and one Uruguayan with the mutation c.1132G>C p. (Asp378His), both mutations occurring in the same codon. The present study enlarges the clinical, morphological and muscle MRI spectrum of AD-HNRNPDL-related myopathies demonstrating the significant particularities of the disease. We describe two new unrelated Argentinean families, carrying the previously reported c.1132G>C p.(Asp378His) HNRNPDL mutation. There was a wide phenotypic spectrum including oligo-symptomatic cases, pure limb girdle muscle involvement or distal lower limb muscle weakness. Scapular winging was the most common finding, observed in all patients. Muscle MRIs of the thigh, at different stages of the disease, showed particular involvement of adductor magnus and vastus besides a constant preservation of the rectus femoris and the adductor longus muscles, defining a novel MRI pattern. Muscle biopsy findings were characterized by the presence of numerous rimmed vacuoles, cytoplasmic bodies, and abundant autophagic material at the histochemistry and ultrastructural levels. HNRNPDL-related LGMD D3 results in a wide range of clinical phenotypes from the classic proximal form of LGMD to a more distal phenotype. Thigh MRI suggests a specific pattern. Codon 378 of HNRNPDL gene can be considered a mutation hotspot for HNRNPDL-related myopathy. Pathologically, the disease can be classified among the autophagic rimmed vacuolar myopathies as with the other multisystem proteinopathies.
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Acknowledgements
This work has been financially supported by Association Françaisecontre les Myopathies (AFM-Telethon), Association Institut de Myologie (AIM), Assistance Publique-Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la RechercheMédicale (INSERM), Sorbonne Université, Centre National de la RechercheScientifique (CNRS), University of Strasbourg, the France Génomique National infrastructure funded as part of the Investissementsd’ Avenir program managed by the AgenceNationale pour la Recherche (ANR-10-INBS-09) and by Fondation Maladies Rares within the frame of the “Myocapture” sequencing project, the Fondation pour la RechercheMédicale.
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Berardo, A., Lornage, X., Johari, M. et al. HNRNPDL-related muscular dystrophy: expanding the clinical, morphological and MRI phenotypes. J Neurol 266, 2524–2534 (2019). https://doi.org/10.1007/s00415-019-09437-3
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DOI: https://doi.org/10.1007/s00415-019-09437-3