肢带型肌营养不良
肌肉活检
肌病
大腿
肌营养不良
病理
医学
解剖
近端肌无力
表型
神经肌肉疾病
生物
活检
遗传学
疾病
内科学
基因
作者
Andres Berardo,Xavière Lornage,Mridul Johari,Teresinha Evangelista,Claudia Cejas,Fabio Barroso,Alberto Dubrovsky,Mai Thao Bui,Guy Brochier,M. Saccoliti,Johann Böhm,Bjarne Udd,Jocelyn Laporte,Norma B. Romero,Ana Lia Taratuto
标识
DOI:10.1007/s00415-019-09437-3
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI