Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order Amish

Muscle Nerve. 2015 May;51(5):767-72. doi: 10.1002/mus.24528. Epub 2015 Feb 17.

Abstract

Introduction: 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.

Keywords: Amish nemaline myopathy (ANM); TNNT1; congenital myopathy; nemaline myopathy; slow skeletal muscle troponin T1.

Publication types

  • Case Reports

MeSH terms

  • Biopsy
  • Child, Preschool
  • Exons / genetics
  • Hispanic or Latino / genetics
  • Homozygote
  • Humans
  • Male
  • Muscle, Skeletal / pathology
  • Mutation / genetics*
  • Myopathies, Nemaline / diagnosis
  • Myopathies, Nemaline / genetics*
  • Pedigree
  • Troponin I / genetics*

Substances

  • TNNI1 protein, human
  • Troponin I

Supplementary concepts

  • Nemaline myopathy 5