PMID- 27066587
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160412
LR  - 20201001
IS  - 2376-7839 (Print)
IS  - 2376-7839 (Electronic)
IS  - 2376-7839 (Linking)
VI  - 2
IP  - 1
DP  - 2016 Feb
TI  - Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain 
      of STIM1.
PG  - e50
LID - 10.1212/NXG.0000000000000050 [doi]
LID - e50
AB  - OBJECTIVE: To identify the gene mutation of tubular aggregate myopathy (TAM) and 
      gain mechanistic insight into the pathogenesis of the disorder. METHODS: We 
      described a family affected by autosomal dominant TAM and performed exome and 
      Sanger sequencing to identify mutations. We further analyzed the functional 
      significance of the identified mutation by expression studies and intracellular 
      Ca(2+) measurements. RESULTS: A 42-year-old man presented with slowly progressive 
      muscle weakness and atrophy in all 4 limbs and the trunk. Muscle biopsy and 
      microscopic examination revealed tubular aggregates in his skeletal muscle. 
      Genetic analysis of this family identified a novel heterozygous mutation, 
      c.1450_1451insGA (p.Ile484ArgfsX21), in stromal interaction molecule 1 (STIM1), a 
      Ca(2+) sensor in sarcoplasmic reticulum. We transfected cultured cells with STIM1 
      and demonstrated that the mutant STIM1 exhibited aggregation-like appearance in 
      shrunk cytoplasm. Furthermore, we revealed that the intracellular Ca(2+) influx 
      is decreased by the mutant STIM1. CONCLUSIONS: The novel mutation 
      p.Ile484ArgfsX21 is located in the cytoplasmic C-terminal inhibitory domain 
      (CTID) of STIM1. However, all mutations reported so far in TAM reside in the 
      luminal N-terminal EF hand region. The aggregation-like appearance of STIM1 and 
      the decreased intracellular Ca(2+) influx in cells transfected with CTID mutant 
      are in sharp contrast to these previous reports. Taken together, these findings 
      indicate that mutations of STIM1 cause TAM through the dysregulation of Ca(2+) 
      homeostasis.
FAU - Okuma, Hidehiko
AU  - Okuma H
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Saito, Fumiaki
AU  - Saito F
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Mitsui, Jun
AU  - Mitsui J
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Hara, Yuji
AU  - Hara Y
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Hatanaka, Yuki
AU  - Hatanaka Y
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Ikeda, Miki
AU  - Ikeda M
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Shimizu, Teruo
AU  - Shimizu T
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Matsumura, Kiichiro
AU  - Matsumura K
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Shimizu, Jun
AU  - Shimizu J
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Tsuji, Shoji
AU  - Tsuji S
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
FAU - Sonoo, Masahiro
AU  - Sonoo M
AD  - Department of Neurology (H.O., F.S., Y. Hatanaka, M.I., K.M., M.S.), School of 
      Medicine, and Department of Sport and Medical Science (T.S.), Faculty of Medical 
      Technology, Teikyo University, Tokyo, Japan; Department of Neurology (J.M., J.S., 
      S.T.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; and 
      Department of Synthetic Chemistry and Biological Chemistry (Y. Hara), Graduate 
      School of Engineering, Kyoto University, Kyoto, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160201
PL  - United States
TA  - Neurol Genet
JT  - Neurology. Genetics
JID - 101671068
PMC - PMC4817897
EDAT- 2016/04/12 06:00
MHDA- 2016/04/12 06:01
PMCR- 2016/02/01
CRDT- 2016/04/12 06:00
PHST- 2015/03/17 00:00 [received]
PHST- 2015/12/07 00:00 [accepted]
PHST- 2016/04/12 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2016/04/12 06:01 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - NG2015000034 [pii]
AID - 10.1212/NXG.0000000000000050 [doi]
PST - epublish
SO  - Neurol Genet. 2016 Feb 1;2(1):e50. doi: 10.1212/NXG.0000000000000050. eCollection 
      2016 Feb.