a novel autosomal dominant inclusion body myopathy linked to 7q22.1-31.1一种常染色体显性包涵体肌病与7 q22.1 - 31.1.pdfVIP

A Novel Autosomal Dominant Inclusion Body Myopathy Linked to 7q22.1-31.1 1. 2,3. 1 2 2 1 2 1 2 Yan Lu , Xingang Li , Min Wang , Xin Li , Feng Zhang , Yun Li , Meng Zhang , Yuwei Da *, Jun Yu * , Jianping Jia1 1 Department of Neurology, Capital Medical University, Xuan Wu Hospital, Beijing, People’s Republic of China, 2 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing,People’s Republic of China, 3 Graduate School of Chinese Academy of Sciences, Beijing, People’s Republic of China Abstract We describe a novel autosomal dominant hereditary inclusion body myopathy (HIBM) that clinically mimics limb girdle muscular dystrophy in a Chinese family. We performed a detailed clinical assessment of 36 individuals spanning four generations. The age of onset ranged from the 30s to the 50s. Hip girdle, neck flexion and axial muscle weakness were involved at an early stage. This disease progressed slowly, and a shoulder girdle weakness appeared later in the disease course. Muscle biopsies showed necrotic, regenerating, and rimmed vacuolated fibers as well as congophilic inclusions in some of the fibers. Electron micrograph revealed cytoplasmic inclusions of 15–21 nm filaments. A genomewide scan and haplotype analyses were performed using an Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM), which traced the disease to a new locus on chromosome 7q22.1–31.1 with a maximum multi-point LOD score of 3.65. The critical locus for this unique disorder, which is currently referred to as hereditary inclusion body myopathy 4 (HIBM4), spans 8.78 Mb and contains 65 genes. This localization raises the possibility that one of the genes cluste