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Hereditary inclusion‐body myopathy: Clues on pathogenesis and possible therapy
Author(s) -
Broccolini Aldobrando,
Gidaro Teresa,
Morosetti Roberta,
Mirabella Massimiliano
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21385
Subject(s) - myopathy , pathogenesis , sialic acid , inclusion body myositis , gene , muscle disorder , biology , medicine , genetics , bioinformatics , pathology , immunology , disease
Hereditary inclusion‐body myopathy (h‐IBM), or distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with onset in early adult life and a progressive course leading to severe disability. h‐IBM/DMRV is due to mutations of a gene ( GNE ) that codes for a rate‐limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been unambiguously clarified how GNE gene mutations impair muscle metabolism. Although numerous studies have indicated a key role of hyposialylation of glycoproteins in h‐IBM/DMRV pathogenesis, others have demonstrated new and unpredicted functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h‐IBM/DMRV and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of this disorder. Muscle Nerve, 2009