title: Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order Amish.
abstract: BACKGROUND
  Nemaline myopathy (NM) is a congenital neuromuscular disorder often characterized by hypotonia, facial weakness, skeletal muscle weakness, and the presence of rods on muscle biopsy. A rare form of nemaline myopathy known as Amish Nemaline Myopathy has only been seen in a genetically isolated cohort of Old Order Amish patients who may additionally present with tremors in the first 2-3 months of life.
  
  
  METHODS
  We describe an Hispanic male diagnosed with nemaline myopathy histopathologically and subsequently confirmed by next generation gene sequencing.
  
  
  RESULTS
  Direct sequencing revealed that he is homozygous for a pathogenic nonsense variant c.323C>G (p.S108X) in exon 9 of the TNNT1 gene.
  
  
  CONCLUSIONS
  This report describes a novel pathogenic variant in the TNNT1 gene and represents a nemaline myopathy-causing variant in the TNNT1 gene outside of the Old Order Amish and Dutch ancestry.
authors.affiliation: Department of Neurology, Columbia University, 180 Fort Washington Avenue, New York, New York, 10032, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marra
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Engelstad
authors.forename: Arunkanth
authors.initials: A
authors.lastname: Ankala
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Jahannaz
authors.initials: J
authors.lastname: Dastgir
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Bradford
authors.initials: B
authors.lastname: Coffee
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Chiriboga
mesh_terms: D001706:Biopsy; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D019210:Troponin I / Q000235:genetics*
chemical_list: C581522:TNNI1 protein, human; D019210:Troponin I
keywords: Amish nemaline myopathy (ANM); TNNT1; congenital myopathy; nemaline myopathy; slow skeletal muscle troponin T1