RT Journal Article SR Electronic T1 Clinical phenotype and loss of the slow skeletal muscle troponin T in three new patients with recessive TNNT1 nemaline myopathy JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 602 OP 608 DO 10.1136/jmedgenet-2019-106714 VO 58 IS 9 A1 Justine Géraud A1 Klaus Dieterich A1 John Rendu A1 Emmanuelle Uro Coste A1 Murielle Dobrzynski A1 Pascale Marcorelle A1 Christine Ioos A1 Norma Beatriz Romero A1 Eloise Baudou A1 Julie Brocard A1 Anne-Cécile Coville A1 Julien Fauré A1 Michel Koenig A1 Raul Juntas Morales A1 Emmanuelle Lacène A1 Angéline Madelaine A1 Isabelle Marty A1 Henri Pegeot A1 Corinne Theze A1 Aurore Siegfried A1 Mireille Cossee A1 Claude Cances YR 2021 UL http://jmg.bmj.com/content/58/9/602.abstract AB Background Congenital nemaline myopathies are rare pathologies characterised by muscle weakness and rod-shaped inclusions in the muscle fibres.Methods Using next-generation sequencing, we identified three patients with pathogenic variants in the Troponin T type 1 (TNNT1) gene, coding for the troponin T (TNT) skeletal muscle isoform.Results The clinical phenotype was similar in all patients, associating hypotonia, orthopaedic deformities and progressive chronic respiratory failure, leading to early death. The anatomopathological phenotype was characterised by a disproportion in the muscle fibre size, endomysial fibrosis and nemaline rods. Molecular analyses of TNNT1 revealed a homozygous deletion of exons 8 and 9 in patient 1; a heterozygous nonsense mutation in exon 9 and retention of part of intron 4 in muscle transcripts in patient 2; and a homozygous, very early nonsense mutation in patient 3.Western blot analyses confirmed the absence of the TNT protein resulting from these mutations.Discussion The clinical and anatomopathological presentations of our patients reinforce the homogeneous character of the phenotype associated with recessive TNNT1 mutations. Previous studies revealed an impact of recessive variants on the tropomyosin-binding affinity of TNT. We report in our patients a complete loss of TNT protein due to open reading frame disruption or to post-translational degradation of TNT.All data relevant to the study are included in the article or uploaded as supplementary information.