P-03

Recessive TTN truncating mutation define a novel antenatal severe form of “CAP-myopathy” in absence of heart disease

Ana Fernández-Marmiesse^I; M. Carmen Carrascosa-Romero^II; Iria Roca^I; Sofia Gouveia^I; Mª Luz Couce Pico^I

^IHospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
^IINeuropediatric Unit, Complejo Universitario Hospitalario de Albacete, Albacete, Spain

amarmiesse@gmail.com

Background: Arthrogryposis     multiplex     congenital (AMC)  is  defined  as  multiple  congenital  non-progressive joint contractures involving more than one area of the body. Amyoplasia, is the most common type of arthrogryposis, characterized  by  a  generalized  replacement  of  skeletal muscle by dense fibrous tissue and fat. “CAP myopathy” is a rare congenital myopathy characterized by cap structures consisting of disarranged thin filaments with enlarged Z discs, located at the periphery of the muscle fiber. Four genes have been associated (ACTA1, TPM2, TPM3 and NEB). To date TTN gene has never been associated with “CAP-myopathy”.

Methods and results: We report a newborn presenting with  AMC,  severe  axial  hypotonia,  and  muscular  biopsy compatible with amyoplasia and “CAP-myopathy”. A novel homozygous truncating mutation (c.38661_38669del) in the PEVK segment of TTN gene was detected by targeted next generation sequencing assay.

Conclusion: We report for first time an association between TTN gene and “CAP-myopathy”, showing that mutations in this gene should be considered in all congenital myopathies even if cardiac involvement is absent. We show also the first described TTN mutation which leads to totally sarcomere disintegration and placed in an exon only transcribed in fetal period (isoform IC).

Keywords: Arthrogryposis multiplex congenital, amyoplasia, “CAP-myopathy”, targeted NGS, TTN-PEVK