Abstract:

A middle-aged Japanese man presented with slowly progressive asymmetric weakness of legs and arm but had neither ptosis nor dysphagia. He had a family history of similar condition suggestive of autosomal dominant inheritance. A muscle biopsy showed mixture of neurogenic atrophy and myopathy with rimmed vacuoles. Furthermore we found intranuclear inclusions that had a fine structure mimicking that of inclusions reported in oculopharyngeal muscular dystrophy (OPMD). Immunohistochemical staining for polyadenylate-binding nuclear protein 1, which is identified within the nuclear inclusions of OPMD, demonstrated nuclear positivity in this case. However, OPMD was thought unlikely based on the clinical features and results of genetic analyses. Instead, a novel mutation in valosin-containing protein, c.376A>T (p.Ile126Phe), was revealed. A diagnosis of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia was made. This is the first report of polyadenylate-binding nuclear protein 1-positive nuclear inclusions in the muscle of this condition.

日本語要旨:

骨パジェット病および前頭側頭型痴呆を伴う封入体ミオパチー(IBMPFD)であるにも関わらず、眼咽頭型筋ジストロフィー(OPMD)に特有な核内封入体が存在する症例を報告した。常染色体優性遺伝を示唆する家族歴があり、緩徐進行性で非対称な四肢遠位筋力低下を示し、眼瞼下垂や嚥下障害はない。筋病理では、神経原性萎縮とミオパチーの混合所見を示し、縁取り空胞が見られた。核内封入体はOPMD特有なものに類似する微細構造を持ち、免疫染色でPABPN1タンパク質陽性であった。臨床的特徴と遺伝子解析からOPMDが否定される一方、VCPタンパク質に c.376A> T(p.Ile126Phe)変異が見つかった。