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ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy.
Park, Hyung Jun; Hong, Young Bin; Choi, Young-Chul; Lee, Jinho; Kim, Eun Ja; Lee, Ji-Su; Mo, Won Min; Ki, Soo Mi; Kim, Hyo In; Kim, Hye Jin; Hyun, Young Se; Hong, Hyun Dae; Nam, Kisoo; Jung, Sung Chul; Kim, Sang-Beom; Kim, Se Hoon; Kim, Deok-Ho; Oh, Ki-Wook; Kim, Seung Hyun; Yoo, Jeong Hyun; Lee, Ji Eun; Chung, Ki Wha; Choi, Byung-Ok.
Afiliación
  • Park HJ; Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, South Korea.
  • Hong YB; Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
  • Choi YC; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Lee J; Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
  • Kim EJ; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Lee JS; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Mo WM; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
  • Ki SM; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Kim HI; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
  • Kim HJ; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
  • Hyun YS; Department of Biological Science, Kongju National University, Gongju, South Korea.
  • Hong HD; Department of Biological Science, Kongju National University, Gongju, South Korea.
  • Nam K; Department of Biological Science, Kongju National University, Gongju, South Korea.
  • Jung SC; Department of Chemistry, New York University, New York, NY.
  • Kim SB; Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, South Korea.
  • Kim SH; Department of Neurology, Kyung Hee University College of Medicine, Kangdong Hospital, Seoul, South Korea.
  • Kim DH; Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
  • Oh KW; Department of Bioengineering, University of Washington, Seattle, WA.
  • Kim SH; Department of Neurology, College of Medicine, Hanyang University, Seoul, South Korea.
  • Yoo JH; Department of Neurology, College of Medicine, Hanyang University, Seoul, South Korea.
  • Lee JE; Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, South Korea.
  • Chung KW; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
  • Choi BO; Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea.
Ann Neurol ; 79(2): 231-43, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26506222
OBJECTIVE: Distal myopathy is a heterogeneous group of muscle diseases characterized by predominant distal muscle weakness. A study was done to identify the underlying cause of autosomal recessive adolescent onset distal myopathy. METHODS: Four patients from 2 unrelated Korean families were evaluated. To isolate the genetic cause, exome sequencing was performed. In vitro and in vivo assays using myoblast cells and zebrafish models were performed to examine the ADSSL1 mutation causing myopathy pathogenesis. RESULTS: Patients had an adolescent onset distal myopathy phenotype that included distal dominant weakness, facial muscle weakness, rimmed vacuoles, and mild elevation of serum creatine kinase. Exome sequencing identified completely cosegregating compound heterozygous mutations (p.D304N and p.I350fs) in ADSSL1, which encodes a muscle-specific adenylosuccinate synthase in both families. None of the controls had both mutations, and the mutation sites were located in well-conserved regions. Both the D304N and I350fs mutations in ADSSL1 led to decreased enzymatic activity. The knockdown of the Adssl1 gene significantly inhibited the proliferation of mouse myoblast cells, and the addition of human wild-type ADSSL1 reversed the reduced viability. In an adssl1 knockdown zebrafish model, muscle fibers were severely disrupted, which was evaluated by myosin expression and birefringence. In these conditions, supplementing wild-type ADSSL1 protein reversed the muscle defect. INTERPRETATION: We suggest that mutations in ADSSL1 are the novel genetic cause of the autosomal recessive adolescent onset distal myopathy. This study broadens the genetic and clinical spectrum of distal myopathy and will be useful for exact molecular diagnostics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenilosuccinato Sintasa / Miopatías Distales Límite: Adult / Animals / Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Ann Neurol Año: 2016 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenilosuccinato Sintasa / Miopatías Distales Límite: Adult / Animals / Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Ann Neurol Año: 2016 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos