Details

Autor(en) / Beteiligte

• Wang, Guangyu
• Zhao, Dandan
• Yan, Chuanzhu
• Lin, Pengfei

Titel

Exon skipping caused by splicing mutation in TNNT1 nemaline myopathy

Ist Teil von

• Journal of human genetics, 2023-02, Vol.68 (2), p.97-101

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• The TNNT1 gene encoding the slow skeletal muscle TnT has been identified as a causative gene for nemaline myopathy. TNNT1 nemaline myopathy is mainly characterized by neonatal-onset muscle weakness, pectus carinatum and respiratory insufficiency. Herein, we report on a Chinese girl with TNNT1 nemaline myopathy with mild clinical phenotypes without thoracic deformities or decreased respiratory function. Muscle biopsy showed moderate to marked type 1 fiber atrophy and nemaline rods. Next-generation sequencing identified the compound heterozygous c. 587dupA (p. D196Efs*41) and c. 387+5G>A mutations in the TNNT1 gene according to the transcript NM_003283.4. RNA sequencing revealed complete exon 9 skipping caused by the c. 387+5G>A mutation. Through quantitative PCR, we found that both the truncation c. 587dupA (p. D196Efs*41) and the splicing c. 387+5G>A mutations triggered nonsense-mediated mRNA decay (NMD). Western blotting showed the residual amount of the truncated TNNT1 protein by deletion of exon 9, which may ameliorate the disease to some extent.