title: DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions.
abstract: DNAJB6, which encodes DnaJ homolog, subfamily B, member 6 (DNAJB6) was recently identified as a causative gene for limb-girdle muscular dystrophy type 1D (LGMD1D). DNAJB6 is a member of heat shock protein 40 and contains a J domain, G/F domain and C-terminal domain. Only three different mutations have been identified in 11 families. In this study, we identified seven Japanese individuals from four unrelated families who carried a DNAJB6 mutation. We found a novel p.Phe96Ile substitution and a previously reported p.Phe96Leu change in the G/F domain of DNAJB6. All affected individuals showed slowly progressive muscle weakness, mainly in their legs, and their muscle pathology showed cytoplasmic inclusions and rimmed vacuoles. Our immunohistochemical analysis detected cytoplasmic accumulations associated with chaperone-assisted selective autophagy together with intranuclear accumulations of DNAJB6 and heat shock 22-kD protein 8 (HSPB8). This is the first report of Asian patients with LGMD1D. Our new findings may contribute to understanding the pathological mechanisms of this myopathy.
authors: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
authors: Takatoshi
authors: T
authors: Sato
authors: Yukiko K
authors: YK
authors: Hayashi
authors: Yasushi
authors: Y
authors: Oya
authors: Tomoyoshi
authors: T
authors: Kondo
authors: Kazuma
authors: K
authors: Sugie
authors: Daita
authors: D
authors: Kaneda
authors: Hideki
authors: H
authors: Houzen
authors: Ichiro
authors: I
authors: Yabe
authors: Hidenao
authors: H
authors: Sasaki
authors: Satoru
authors: S
authors: Noguchi
authors: Ikuya
authors: I
authors: Nonaka
authors: Makiko
authors: M
authors: Osawa
authors: Ichizo
authors: I
authors: Nishino
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics* / Q000473:pathology; D045586:Intranuclear Inclusion Bodies / Q000235:genetics* / Q000473:pathology; D007564:Japan; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics
chemical_list: C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases