Congenital myopathies constitute a very heterogeneous group of neuromuscular diseases both clinically and genetically. They are related to the presence of intrinsic lesions or the accumulation of inclusions inside the muscle fiber. They are classically described as responsible for global hypotonia, little or no selective, and almost never progressive. Nemaline myopathies (also called rod myopathies) are among the most common of these diseases and have been the most studied to date. Nearly ten genes are the direct cause, including the TNNT1 gene which encodes the muscle isoform of troponin T1 and is therefore involved in the proper functioning of the contractile apparatus. The first mutations of the TNNT1 gene were reported in 2000 in the Amish community in the United States.
High-throughput sequencing (NGS for next-generation sequencing) lends itself very well to the simultaneous exploration of all these genes, as illustrated by this article by French clinicians and biologists published in September 2020. They report the first three cases of recessive mutations of the TNNT1 gene in French pediatric patients. The clinical picture was evaluated serious from birth with, in each case, premature death in the first few months to first few years of life, either suddenly or as a result of respiratory complications. In these aspects, the picture was comparable to data reported in the literature. The mutations identified in the TTNT1 gene in NGS were confirmed on the muscle tissue samples, in particular by Western blot.
Clinical phenotype and loss of the slow skeletal muscle troponin T in three new patients with recessive TNNT1 nemaline myopathy. Géraud J, Dieterich K, Rendu J, Uro Coste E, Dobrzynski M, Marcorelle P, Ioos C, Romero NB, Baudou E, Brocard J, Coville AC, Fauré J, Koenig M, Juntas Morales R, Lacène E, Madelaine A, Marty I, Pegeot H, Theze C, Siegfried A, Cossee M, Cances C. J Med Genet. 2020 Sep 29:jmedgenet-2019-106714. doi: 10.1136/jmedgenet-2019-106714. Epub ahead of print. PMID: 32994279.