SYNE-1 and SYNE-2 mutations: expanding the genotype and phenotype spectrum of nesprinopathies

Elenco Abstract

Marta Cheli

SYNE-1 and SYNE-2 mutations: expanding the genotype and phenotype spectrum of nesprinopathies

Autori

MARTA CHELI (DEPARTMENT OF NEUROSCIENCE, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA – NEUROLOGO)
GIULIA MARCHETTO (DEPARTMENT OF NEUROSCIENCE, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA – )
ANNA RUBEGNI (IRCCS FONDAZIONE STELLA MARIS, PISA – )
SARA GIBERTINI (NEUROIMMUNOLOGY AND NEUROMUSCULAR DISEASES UNIT, FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA, MILAN – )
SERENA BARATTO (PAEDIATRIC NEUROLOGY AND NEUROMUSCULAR DISORDERS UNIT, DEPARTMENT OF NEUROSCIENCES, REHABILITATION, OPHTHALMOLOGY, GENETICS, MATERNAL AND CHILD HEALTH, UNIVERSITY OF GENOA, ISTITUTO GIANNINA GASLINI, GENOA – )
CLAUDIO BRUNO (TRANSLATIONAL AND EXPERIMENTAL MYOLOGY CENTRE, ISTITUTO GIANNINA GASLINI, GENOA – )
MASSIMILIANO FILOSTO (DEPARTMENT OF CLINICAL AND EXPERIMENTAL SCIENCES, NEMO-BRESCIA CLINICAL CENTER FOR NEUROMUSCULAR DISEASES, UNIVERSITY OF BRESCIA, BRESCIA – )
CHIARA FIORILLO (PAEDIATRIC NEUROLOGY AND NEUROMUSCULAR DISORDERS UNIT, DEPARTMENT OF NEUROSCIENCES, REHABILITATION, OPHTHALMOLOGY, GENETICS, MATERNAL AND CHILD HEALTH, UNIVERSITY OF GENOA, ISTITUTO GIANNINA GASLINI, GENOA – )
MARINA GRANDIS (IRCCS-OSPEDALE POLICLINICO SAN MARTINO-UOC CLINICA NEUROLOGICA, GENOVA – )
DIEGO LOPERGOLO (DEPARTMENT OF MEDICINE, SURGERY AND NEUROSCIENCES, UNIVERSITY OF SIENA, SIENA – )
MARIA ANTONIETTA MAIOLI (ASL8, CENTRO SCLEROSI MULTIPLA, CAGLIARI – )
ALESSANDRO MALANDRINI (DEPARTMENT OF MEDICINE, SURGERY AND NEUROSCIENCES, UNIVERSITY OF SIENA, SIENA – )
PAOLA MANDICH (IRCCS OSPEDALE POLICLINICO SAN MARTINO-UOC GENETICA MEDICA, GENOVA – )
ROBERTO MASSA (DEPARTMENT OF SYSTEMS MEDICINE, CENTRE OF NEUROMUSCULAR DISORDERS, TOR VERGATA UNIVERSITY, ROME – )
SABRINA MATÀ (CAREGGI UNIVERSITY HOSPITAL, NEUROLOGY UNIT, FLORENCE – )
FEDERICO MELANI (NEUROLOGY UNIT AND NEUROGENETICS LABORATORIES, MEYER CHILDREN HOSPITAL, FLORENCE – )
LUCIANO MERLINI (DEPARTMENT OF BIOMEDICAL AND NEUROMOTOR SCIENCES, UNIVERSITY OF BOLOGNA, BOLOGNA – )
ANDREA MIGNARRI (DEPARTMENT OF MEDICINE, SURGERY AND NEUROSCIENCES, UNIVERSITY OF SIENA, SIENA – )
DANIELE ORSUCCI (UNIT OF NEUROLOGY, SAN LUCA HOSPITAL, LUCCA – )
PATRIZIA SABATELLI (INSTITUTE OF MOLECULAR GENETICS “”LUIGI LUCA CAVALLI-SFORZA””, CNR, BOLOGNA – )
MICHELE SACCHINI (METABOLIC DISEASE UNIT, MEYER CHILDREN’S UNIVERSITY HOSPITAL, FLORENCE – )
ELISA SCHENA (IRCCS ISTITUTO ORTOPEDICO RIZZOLI, 40136 BOLOGNA, ITALY. – )
NILA VOLPI (DEPARTMENT OF MEDICINE, SURGERY AND NEUROSCIENCES, UNIVERSITY OF SIENA, SIENA – )
GIOVANNA LATTANZI (IRCCS ISTITUTO ORTOPEDICO RIZZOLI, 40136 BOLOGNA, ITALY. – )
LORENZO MAGGI (NEUROIMMUNOLOGY AND NEUROMUSCULAR DISEASES UNIT, FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA, MILAN – )
FILIPPO MARIA SANTORELLI (IRCCS FONDAZIONE STELLA MARIS, PISA – )
PAOLA TONIN (DEPARTMENT OF NEUROSCIENCE, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA – )
DENISE CASSANDRINI (IRCCS FONDAZIONE STELLA MARIS, PISA – )
GAETANO VATTEMI (DEPARTMENT OF NEUROSCIENCE, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA -)

Presentatore

MARTA CHELI (DEPARTMENT OF NEUROSCIENCE, BIOMEDICINE AND MOVEMENT SCIENCES, UNIVERSITY OF VERONA, VERONA)

Modalità

Oral Communication

Abstract

Nesprins are a family of spectrin-repeat proteins located at the nuclear envelope which play an important role in nuclear morphology and mechano-transduction. Nesprin-1 and Nesprin-2, encoded by the synaptic nuclear envelope SYNE-1 and SYNE2, are highly expressed in cardiac and skeletal muscle. Mutations in SYNE1 have been associated with the autosomal dominant EDMD4, congenital muscular dystrophy, and arthrogryposis multiplex congenita while mutations in SYNE2 only with EDMD5. In this study, we aimed at defining the clinical characteristics, histopathological features and molecular profile of 55 patients carrying single nucleotide variants in SYNE1 and SYNE2 genes. Multiple algorithms were used to predict the deleteriousness of the variants and only variants with CADD scores ≥20 were selected. In our cohort 56% of patients were women; 60% of patients had late onset myopathy and 23% of patients presented with EDMD-like phenotype. In 80% of patients muscle biopsy showed myopathic signs, with dystrophic changes in the 28% of cases. The subcellular localization of Nesprin-1 and -2 and their co-localization with Emerin, an inner nuclear membrane protein, were evaluated by immunofluorescence in muscle tissue from 21 patients and neither reduced nuclear staining nor mislocalization of both nesprins were detected. Our data provide a further insight into the clinical phenotypes and muscle pathology associated with SYNE1 or SYNE2 mutations and suggest that immunohistochemistry does not represent a useful diagnostic tool.