ArticleHuman molecular genetics2018
TNNT1 nemaline myopathy: natural history and therapeutic frontier.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data.Journal of child neurology · 2022Pooled it
- Potential cytotoxicity of truncated slow skeletal muscle troponin T (ssTnT) in a loss of function TNNT1 myopathy mouse model.The FEBS journal · 2025Article
- Elimination of myotonia improves myopathy in a muscleblind knockout model of myotonic dystrophy.bioRxiv : the preprint server for biology · 2025Article
- A homozygous single-nucleotide variant inJournal of neuromuscular diseases · 2025Article
- Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model.Diseases (Basel, Switzerland) · 2025Article
- Pathogenic TNNT1 variants are associated with aberrant thin filament compliance and myofibre hyper-contractility.The Journal of physiology · 2025Article
- Genomic sequencing: the case for equity of care in the era of personalized medicine.Pediatric research · 2025Review
- Article
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- A rare TNNT1 gene variant causing creatine kinase elevation in nemaline myopathy: c.271_273del (p.Lys91del).Genes & genomics · 2024Article
- Role of the interaction between troponin T and AMP deaminase by zinc bridge in modulating muscle contraction and ammonia production.Molecular and cellular biochemistry · 2024Review
- WiTNNess: An international natural history study of infantile-onset TNNT1 myopathy.Annals of clinical and translational neurology · 2023Observational
- Transcriptional and open chromatin analysis of bovine skeletal muscle development by single-cell sequencing.Cell proliferation · 2023Article
- Cross-sectional survey on genetic testing utilization and perceptions in Wisconsin Amish and Mennonite communities.Journal of community genetics · 2023Article
- Article
- Single-cell RNA sequencing in silent corticotroph tumors confirms impaired POMC processing and provides new insights into their invasive behavior.European journal of endocrinology · 2022Article
- Clinical and genetic features of infancy-onset congenital myopathies from a Chinese paediatric centre.BMC pediatrics · 2022Article
- The distal arthrogryposis-linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3.Journal of clinical laboratory analysis · 2021Article
- Clinical phenotype and loss of the slow skeletal muscle troponin T in three new patients with recessive TNNT1 nemaline myopathy.Journal of medical genetics · 2021Article
- Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics.International journal of molecular sciences · 2021Review
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Authors and funding
8 authors.
Funding
Abstract
We describe the natural history of 'Amish' nemaline myopathy (ANM), an infantile-onset, lethal disease linked to a pathogenic c.505G>T nonsense mutation of TNNT1, which encodes the slow fiber isoform of troponin T (TNNT1; a.k.a. TnT). The TNNT1 c.505G>T allele has a carrier frequency of 6.5% within Old Order Amish settlements of North America. We collected natural history data for 106 ANM patients born between 1923 and 2017. Over the last two decades, mean age of molecular diagnosis was 16 ± 27 days. TNNT1 c.505G>T homozygotes were normal weight at birth but failed to thrive by age 9 months. Presenting neonatal signs were axial hypotonia, hip and shoulder stiffness, and tremors, followed by progressive muscle weakness, atrophy and contractures. Affected children developed thoracic rigidity, pectus carinatum and restrictive lung disease during infancy, and all succumbed to respiratory failure by 6 years of age (median survival 18 months, range 0.2-66 months). Muscle histology from two affected children showed marked fiber size variation owing to both Type 1 myofiber smallness (hypotrophy) and Type 2 fiber hypertrophy, with evidence of nemaline rods, myofibrillar disarray and vacuolar pathology in both fiber types. The truncated slow TNNT1 (TnT) fragment (p.Glu180Ter) was undetectable in ANM muscle, reflecting its rapid proteolysis and clearance from sarcoplasm. Similar functional and histological phenotypes were observed in other human cohorts and two transgenic murine models (Tnnt1-/- and Tnnt1 c.505G>T). These findings have implications for emerging molecular therapies, including the suitably of TNNT1 gene replacement for newborns with ANM or other TNNT1-associated myopathies.
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