title: Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1).
abstract: BACKGROUND
  Nemaline myopathy is a rare disorder characterized by skeletal muscle weakness of varying severity and onset, with the presence of nemaline rods on muscle biopsy. Congenital nemaline body myopathy due to mutations in TNNT1 has hitherto only been described as a result of a single founder mutation in patients of Amish origin and in 2 other individuals with different recessive mutations.
  
  
  METHODS
  Autozygosity mapping and whole exome sequencing were applied after we identified 9 Palestinian patients from 7 unrelated families who have nemaline myopathy.
  
  
  RESULTS
  All patients were homozygous for a novel complex rearrangement of the TNNT1 gene (c.574_577delinsTAGTGCTGT | NM_003283) leading to C-terminal truncation of the protein (p.L203* | NP_003274.3). Their clinical course was remarkable for early respiratory failure and striking stiffness of the cervical spine.
  
  
  CONCLUSIONS
  This report exemplifies the utility of combining autozygosity mapping and whole exome sequencing and expands the phenotype associated with TNNT1 mutations.
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Ulla Najwa
authors: UN
authors: Abdulhaq
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Mohannad
authors: M
authors: Daana
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Talia
authors: T
authors: Dor
authors: Department of Pathology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yakov
authors: Y
authors: Fellig
authors: Alyn Hospital Pediatric and Adolescent Rehabilitation Center, Jerusalem, Israel.
authors: Sharon
authors: S
authors: Eylon
authors: Klinik für Pädiatrie Neurologie and NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany.
authors: Markus
authors: M
authors: Schuelke
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Avraham
authors: A
authors: Shaag
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Orly
authors: O
authors: Elpeleg
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.|Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Simon
authors: S
authors: Edvardson
mesh_terms: D018912:Arabs / Q000235:genetics*; D002675:Child, Preschool; D004576:Electromyography / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D020107:Troponin T / Q000235:genetics*
chemical_list: D020107:Troponin T
keywords: TNNT1; autozygosity mapping; congenital myopathy; nemaline body myopathy; whole exome sequencing