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A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency.

ABSTRACT: Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Immunohistochemistry and Western blotting revealed a marked reduction of fast myosin heavy chain isoforms. This is the first observation of a titinopathy suggesting that titin defect leads to secondary loss of fast myosin heavy chain isoforms.

SUBMITTER: Perrin A

PROVIDER: S-EPMC7261750 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency.

Perrin Aurélien A Metay Corinne C Villanova Marcello M Carlier Robert-Yves RY Pegoraro Elena E Juntas Morales Raul R Stojkovic Tanya T Richard Isabelle I Richard Pascale P Romero Norma B NB Granzier Henk H Koenig Michel M Malfatti Edoardo E Cossée Mireille M

Annals of clinical and translational neurology 20200419 5

Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament lo ...[more]

PMID: 32307885

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