PUBLICATION

TNNT1 myopathy with novel compound heterozygous mutations

Authors
Lee, S., Eum, J., Park, S., Ki, S., Hwang, B.J., Kee, Y., Chae, J.H.
ID
ZDB-PUB-220216-21
Date
2021
Source
Neuromuscular disorders : NMD   32(2): 176-184 (Journal)
Registered Authors
Eum, Juneyong, Kee, Yun
Keywords
High-throughput nucleotide sequencing, Nemaline myopathy 5, TNNT1, Zebrafish model
MeSH Terms
  • Adolescent
  • Animals
  • Humans
  • Male
  • Muscle, Skeletal/pathology
  • Mutation
  • Myopathies, Nemaline*/genetics
  • Phenotype
  • Troponin T/genetics*
  • Zebrafish*
PubMed
35165004 Full text @ Neuromuscul. Disord.
Abstract
Nemaline myopathies are clinically and genetically heterogeneous disorders caused by several different genes. One of them is TNNT1, which was initially described in Amish families and has not been reported in Asian populations. Although most TNNT1 myopathies are caused by loss-of-function mutations, several recent studies have shown that missense mutations can also be pathogenic. A 16-year-old Korean boy with progressive muscle weakness visited the Seoul National University Hospital. He showed generalized myopathy, which was predominant in the paraspinal and neck muscles. Moreover, nemaline rods were observed in a muscle biopsy. Whole-exome sequencing of DNA samples of the patient and his younger brother, who had a similar phenotype, revealed novel compound heterozygous mutations in TNNT1 (c.724G>C (p.Ala242Pro) and c.611+1G>A). Sanger sequencing of cDNA extracted from muscle samples of the patient confirmed partial or total skipping of exon 11 in the splicing variant. The impact of the missense variant on muscle integrity and locomotor activity was verified using a zebrafish loss-of-function model. Here, we reported novel familial cases of TNNT1 myopathy with intermediate clinical presentations caused by compound heterozygous mutations and demonstrated their functional defects using an animal model.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping