Acta Neuropathologica: Misalmed variation in TTN-related congenital myopathy

The giant muscular protein titin guides the precise submuscular joint positions of hundreds of other myoglobins, acting as the basic structural integrator of transverse muscle joints in the heart and skeletal muscles.
Titin is a protein longer than 1 m and with a molecular weight of more than 3 MDa, encoded by the TTN gene, which combines about 100 kb transcripts of 364 exons in a 300 kb gene.
the protein consists of 132 fibrous-connected protein-3 (Fn3) domains, a kinase domain and up to 169 immunoglobulin (Ig) domains, as well as non-structural regions.
Recent studies have shown that TTN mutations have become the main cause of explicit and recessive hereditary myopathy, and their scope is widespread and expanding, including tibia muscular dystrophy (TMD), muscular dystrophy 2 J (LGMD2J), hereditary myopathy with early respiratory failure (HMERF), Salih myopathy, central transparent myopathy (CNM), heart disease core myopathy, and so on.
mutations in the TTN-coded myoglobin titin are becoming a common cause of myopathy.
, however, the diagnosis of TTN-related myopathy is not usually simple due to clinical pathological overlap with other myopathy and the prevalence of TTN mutations in the control population.
presents a pathogenic approach to diagnosing TTN-related myopathy and determining the pathogenicity of TTN misalmical variations by combining clinical pathology, genetics, and biophysics.
The study included 30 patients from 23 families with primary TTN-related congenital myopathy (CM) and two short-cut variants, or one amputated and one misaltered TTN variant, or one TTN-variant pure ensember.
19 of them were men and 11 were women.
27 patients are still alive and 3 have died (10 weeks, 3 months and 54 years of age).
the age range of the last follow-up (or death) was 10 to 71 years (median was 19 years).
14 patients had a family history of neuromuscular disease, and 11 patients had a family history of first-degree relative heart disease, including confirmed heart disease and/or unexplained sudden death.
no patient had skeletal myopathy.
found that TTN-related myopathy overlaps with other myopathy to a considerable extent, but strongly suggests a combination of certain clinical pathological characteristics.
clinical manifestations of the disease are clinically characterized by different progressions in weakness, contractions, scolio convexity and respiratory symptoms at birth, but the ophthalmology remains.
heart is affected depends on the location.
biophysical analysis showed that the error mutations associated with CMs were highly unstable and played a role when expressed in a short background or purity.
Rees, M., Nikoopour, R., Fukuzawa, A. et al. Making sense of missense variants in TTN-related congenital myopathies. Acta Neuropathol (2021). Network Source: Network Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Met Medical" or "Source: MedSci Original" are owned by Metz Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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