Targeted Next-Generation Sequencing Reveals Novel TTN Mutations Causing Recessive Distal Titinopathy

Data de publicació: 01/11/2017 Data Ahead of Print: 29/10/2016

Autors de IIS La Fe

Juan Jesús Vílchez Padilla

Autor
Nuria Muelas Gómez

Autor

Autors aliens a IIS La Fe

Evilä A
Palmio J
Vihola A
Savarese M
Tasca G
Penttilä S
Lehtinen S
Jonson PH
De Bleecker J
Rainer P
Auer-Grumbach M
Pouget J
Salort-Campana E
Olive M
Hackman P
Udd B

Grups d'Investigació

Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón

Abstract

Tibial muscular dystrophy (TMD) is the first described human titinopathy. It is a mild adult-onset slowly progressive myopathy causing weakness and atrophy in the anterior lower leg muscles. TMD is caused by mutations in the last two exons, Mex5 and Mex6, of the titin gene (TTN). The first reported TMD mutations were dominant, but the Finnish founder mutation FINmaj, an 11-bp insertion/deletion in Mex6, in homozygosity caused a completely different severe early-onset limb-girdle muscular dystrophy 2J (LGMD2J). Later, we reported that not all TMD mutations cause LGMD when homozygous or compound heterozygous with truncating mutation, but some of them rather cause a more severe TMD-like distal disease. We have now performed targeted next-generation sequencing of myopathy-related genes on seven families from Albania, Bosnia, Iran, Tunisia, Belgium, and Spain with juvenile or early adult onset recessive distal myopathy. Novel mutations in TTN Mex5, Mex6 and A-band exon 340 were identified in homozygosity or compound heterozygosity with a frameshift or nonsense mutation in TTN I- or A-band region. Family members having only one of these TTN mutations were healthy. Our results add yet another entity to the list of distal myopathies: juvenile or early adult onset recessive distal titinopathy.

Dades de la publicació

ISSN/ISSNe:: 0893-7648, 1559-1182
Tipus:: Article
Pàgines:: 7212-7223
DOI:: 10.1007/s12035-016-0242-3
PubMed:: 27796757
Factor d'Impacte:: 1,614 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Evilä A:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.
Palmio J:: Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland
Vihola A:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland
Savarese M:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland

Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
Tasca G:: Institute of Neurology, Policlinico "A. Gemelli" Foundation University Hospital, Rome, Italy

Don Carlo Gnocchi ONLUS Foundation, Milan, Italy
Penttilä S:: Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland
Lehtinen S:: Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland
Jonson PH:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland
De Bleecker J:: Neuromuscular Reference Center and Neurology Department, Ghent University Hospital and St. Lucas General Hospital, University of Ghent, Ghent, Belgium
Rainer P:: Division of Cardiology, Medical University of Graz, Graz, Austria
Auer-Grumbach M:: Department of Orthopaedics, Medical University of Vienna, Vienna, Austria
Pouget J:: Neuromuscular and ALS Reference Center, La Timone Hospital, Aix-Marseille University, FILNEMUS, Marseille, France
Salort-Campana E:: Department of Neurology, Hospital Universitari i Politècnic la Fe, Valencia, Spain
Vílchez, JJ:: Department of Neurology, Hospital Universitari i Politècnic la Fe, Valencia, Spain

Centro De Investigación Biomédica En Red De Enfermedades Raras (CIBERER), Madrid, Spain
Muelas N:: Department of Neurology, Hospital Universitari i Politècnic la Fe, Valencia, Spain

Centro De Investigación Biomédica En Red De Enfermedades Raras (CIBERER), Madrid, Spain
Olive M:: Institute of Neuropathology, Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL-Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
Hackman P:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland
Udd B:: Folkhälsan Institute of Genetics, Biomedicum Helsinki and Department of Medical Genetics, Haartman Institute, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland

Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland

Neurology Department, Vaasa Central Hospital, Vaasa, Finland