Autosomal dominantly inherited myopathy likely caused by the TNNT1 variant p.(Asp65Ala).

Autor: Holling T; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lisfeld J; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Johannsen J; Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Matschke J; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Song F; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Altmeppen HC; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kutsche K; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Sep; Vol. 43 (9), pp. 1224-1233. Date of Electronic Publication: 2022 May 11.
DOI: 10.1002/humu.24397
Abstrakt: Nemaline myopathies (NEMs) are genetically and clinically heterogenous. Biallelic or monoallelic variants in TNNT1, encoding slow skeletal troponin T1 (TnT1), cause NEM. We report a 2-year-old patient and his mother carrying the heterozygous TNNT1 variant c.194A>C/p.(Asp65Ala) that occurred de novo in the mother. Both had muscle hypotrophy and muscle weakness. Muscle pathology in the proband's mother revealed slow twitch type 1 fiber hypotrophy and fast twitch type 2 fiber hypertrophy that was confirmed by a reduced ratio of slow skeletal myosin to fast skeletal myosin type 2a. Reverse transcription polymerase chain reaction and immunoblotting data demonstrated increased levels of high-molecular-weight TnT1 isoforms in skeletal muscle of the proband's mother that were also observed in some controls. In an overexpression system, complex formation of TnT1-D65A with tropomyosin 3 (TPM3) was enhanced. The previously reported TnT1-E104V and TnT1-L96P mutants showed reduced or no co-immunoprecipitation with TPM3. Our studies support pathogenicity of the TNNT1 p.(Asp65Ala) variant.
(© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: