Novel dominant distal titinopathy phenotype associated with copy number variation

Aurélien Perrin (1, 2) , Raul Juntas Morales (2, 3) , Françoise Chapon (4) , Corinne Thèze (2) , Delphine Lacourt (2) , Henri Pégeot (2) , Emmanuelle Uro‐coste (5) , Diane Giovannini (6) , Nicolas Leboucq (2) , Martial Mallaret (6) , Emmeline Lagrange (6) , Valérie Rigau (2, 3) , Karen Gaudon (7) , Pascale Richard (7, 8) , Michel Koenig (1, 2) , Corinne Métay (7, 8) , Mireille Cossée (1, 2)

1 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 INM - Institut des Neurosciences de Montpellier
4 CHU Caen
5 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
6 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
7 Institut de Myologie
8 CHU Pitié-Salpêtrière [AP-HP]

The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out-of-frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant-negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype-genotype association and provides hypotheses for its dominant effects.

Domaines: Sciences du Vivant [q-bio]; Neurosciences [q-bio.NC]

Aurélien Perrin, Raul Juntas Morales, Françoise Chapon, Corinne Thèze, Delphine Lacourt, et al.. Novel dominant distal titinopathy phenotype associated with copy number variation. Annals of Clinical and Translational Neurology, In press, 8 (9), pp.1906-1912. ⟨10.1002/acn3.51434⟩. ⟨hal-03304664⟩