Maria Francesca Di Feo
Differential exon usage predicts disease course in the wide titinopathy spectrum
Autori
- MARIA FRANCESCA DI FEO (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI/ UNIVERSITY OF GENOVA, ITALY – GENETICA MEDICA)
- ALI OGHABIAN (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI – )
- ELLA NIPPALA (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI – )
- FRANCESCA FORZANO (GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, DEP. OF CLINICAL GENETICS, LONDON, UNITED KINGDOM/KING’S COLLEGE LONDON, LONDON, UNITED KINGDOM – GENETICA MEDICA)
- EDOARDO MALFATTI (SERVICE NEUROLOGIE MÉDICALE, CENTRE DE RÉFÉRENCE MALADIES NEUROMUSCULAIRE PARIS-EST-ILE DE FRANCE, CHU RAYMOND-POINCARÉ PARIS OUEST, GARCHES, FRANCE – NEUROLOGIA)
- CLAUDIA CASTIGLIONI (CLINICA MEDS, SANTIAGO DE CHILE, CHILE – NEUROLOGIA)
- MATHIAS GAUTEL (RANDALL CENTRE FOR CELL AND MOLECULAR BIOPHYSICS, MUSCLE BIOPHYSICS, KING’S COLLEGE LONDON BHF CENTRE OF RESEARCH EXCELLENCE, LONDON, UK – )
- HEINZ JUNGBLUTH (RANDALL CENTRE FOR CELL AND MOLECULAR BIOPHYSICS, MUSCLE BIOPHYSICS, KING’S COLLEGE LONDON BHF CENTRE OF RESEARCH EXCELLENCE, LONDON, UK – NEUROLOGIA)
- ILONA KREY (INSTITUTE OF HUMAN GENETICS, UNIVERSITY OF LEIPZIG HOSPITALS AND CLINICS, LEIPZIG, GERMANY – GENETICA MEDICA)
- DAVID GOMEZ ANDRES (CHILD NEUROLOGY UNIT. HOSPITAL UNIVERSITARI VALL D’HEBRON, VALL D’HEBRON RESEARCH INSTITUTE (VHIR), BARCELONA, SPAIN – NEUROLOGIA)
- ANGELA BRADY (NORTH WEST THAMES REGIONAL SERVICE, NORTHWICK PARK AND ST. MARK’S HOSPITALS, HARROW, LONDON, UK – GENETICA MEDICA)
- MARIA IASCONE (LABORATORIO DI GENETICA MEDICA, ASST PAPA GIOVANNI XXIII, BERGAMO, ITALY – GENETICA MEDICA)
- ANNA CEREDA (AMBULATORIO DI GENETICA CLINICA, PEDIATRIA 1 – ASST PAPA GIOVANNI XXIII, BERGAMO – GENETICA MEDICA)
- LIDIA PEZZANI (AMBULATORIO DI GENETICA CLINICA, PEDIATRIA 1 – ASST PAPA GIOVANNI XXIII, BERGAMO – GENETICA MEDICA)
- DANIEL NATERA DE BENITO (NEUROMUSCULAR UNIT, NEUROPAEDIATRICS DEPARTMENT, HOSPITAL SANT JOAN DE DÉU, INSTITUT DE RECERCA SANT JOAN DE DÉU, 08950 BARCELONA, SPAIN – NEUROLOGIA)
- ANDRES NASCIMIENTO OSORIO (NEUROPAEDIATRICS DEPARTMENT, INSTITUT DE RECERCA PEDIÀTRICA HOSPITAL SANT JOAN DE DÉU, BARCELONA, SPAIN – NEUROLOGIA)
- BERTA ESTÉVEZ ARIAS (NEUROMUSCULAR UNIT, DEPARTMENT OF NEUROLOGY, HOSPITAL SANT JOAN DE DÉU, BARCELONA, SPAIN – NEUROLOGIA)
- SERGEI KURBATOV (REGIONAL MEDICAL DIAGNOSTIC CENTRE, VORONEZH, RUSSIA – NEUROLOGIA)
- TANIA ATTIE-BITACH ( UNITÉ D’EMBRYOFOETOPATHOLOGIE, SERVICE D’HISTOLOGIE-EMBRYOLOGIE-CYTOGÉNÉTIQUE, HÔPITAL NECKER-ENFANTS MALADES, APHP, PARIS, FRANCE – )
- SHEELA NAMPOOTHIRI (DEPARTMENT OF PEDIATRIC GENETICS, AMRITA INSTITUTE OF MEDICAL SCIENCES & RESEARCH CENTRE, KERALA, INDIA – )
- ERIN RYAN (GENOMIC DATA / GENETIC COUNSELING, GENEDX, GAITHERSBURG, MARYLAND, USA – GENETICA MEDICA)
- MICHELLE MORROW (GENEDX, GAITHERSBURG, MD, USA – GENETICA MEDICA)
- SVETLANA GOROKHOVA (MARSEILLE MEDICAL GENETICS, AIX MARSEILLE UNIVERSITÉ, FACULTÉ DES SCIENCES MÉDICALES ET PARAMÉDICALES – GENETICA MEDICA)
- BRIGITTE CHABROL (APHM, CHU TIMONE, CENTRE DE REFERENCE DES MALADIES NEUROMUSCULAIRES DE L’ENFANT PACARARE, SERVICE DE NEUROPEDIATRIE, MARSEILLE, FRANCE – )
- JUHA SINISALO ( HELSINKI UNIVERSITY CENTRAL HOSPITAL, HELSINKI, FINLAND – )
- HELI TOLPPANEN (HELSINKI UNIVERSITY CENTRAL HOSPITAL, HELSINKI, FINLAND – CARDIOLOGIA)
- JOHANNA TOLVA (TRANSPLANTATION LABORATORY, DEPARTMENT OF PATHOLOGY, UNIVERSITY OF HELSINKI, HAARTMANINKATU 3, FIN-00014, HELSINKI, FINLAND – )
- FRANCINA MUNELL (UNITAT DE MALALTIES NEUROMUSCULARS PEDIÀTRIQUES HOSPITAL UNIVERSITARI VALL D’HEBRON, BARCELONA – NEUROLOGIA)
- JESSICA CAMACHO SORIANO (HISTOLOGY DEPARTMENT, VALL D’HEBRON UNIVERSITY HOSPITAL, BARCELONA, SPAIN – )
- MARIA ANGELES SANCHEZ DURAN (MATERNAL FETAL MEDICINE UNIT, DEPARTMENT OF OBSTETRICS; UNIVERSITAT AUTÒNOMA DE BARCELONA, HOSPITAL VALL D’HEBRON, BARCELONA, SPAIN – )
- MRIDUL JOHARI (HARRY PERKINS INSTITUTE OF MEDICAL RESEARCH, CENTRE FOR MEDICAL RESEARCH, UNIVERSITY OF WESTERN AUSTRALIA, NEDLANDS, WA, AUSTRALIA – )
- HOMA TAJSHARGHI (SCHOOL OF HEALTH SCIENCES, DIVISION OF BIOMEDICINE, UNIVERSITY OF SKOVDE, SKOVDE, SWEDEN – )
- PETER HACKMAN (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI – )
- BJARNE UDD (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI – NEUROLOGIA)
- MARCO SAVARESE (FOLKHÄLSAN RESEARCH CENTER, UNIVERSITY OF HELSINKI -)
Presentatore
MARIA FRANCESCA DI FEO (FOLKHÄLSAN RESEARCH CENTER, HELSINKI, FINLAND/ UNIVERSITY OF GENOVA, GENOVA, ITALY)
Modalità
Oral Communication
Abstract
“Biallelic truncating variants in TTN (TTNtv) have been associated with a wide spectrum of phenotypes, from prenatal muscle diseases with dysmorphic features to adult-onset muscular dystrophy, with or without cardiac involvement. Due to the size and complexity of the TTN gene, establishing a precise diagnosis and prognosis remains challenging. Since variants combinations in each affected individual are almost unique, precision medicine approaches are required.
We performed RNA sequencing on an internal sample cohort of skeletal and cardiac muscles across developmental stages (prenatal and postnatal), supplemented with publicly available data from ENCODE. Correlations between RNA-seq data and clinical phenotypes were explored in 14 cases with biallelic TTNtv collected from international centers. We identified genotype-phenotype correlations with valuable prognostic implications for each titinopathy patient (whether worsening or improving disease course in prenatal and postnatal life) using percentage spliced in index (PSI) for the involved exons. Notably, in one severe prenatal case, the identified TTNtv were considered unlikely to solely account for the phenotype due to undetectable expression levels in fetal muscles.
This study demonstrates that exon usage provides valuable insight for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for exon usage analysis in many other genetic diseases, since most causative genes undergo alternative splicing.”