New association between the ZASP/LDB3 Pro26Ser variant and inclusion body myositis.

Elenco Abstract

Daniela Piga

New association between the ZASP/LDB3 Pro26Ser variant and inclusion body myositis.

Autori

DANIELA PIGA (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY. – BIOLOGA )
SIMONA ZANOTTI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY. – BIOLOGA )
MICHELA RIPOLONE (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY. – BIOLOGA)
LAURA NAPOLI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY. – BIOLOGA)
PATRIZIA CISCATO (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY. – TECNICO DI LABORATORIO)
SARA GIBERTINI (FONDAZIONE IRCCS ISTITUTO NEUROLOGICO “”CARLO BESTA””, NEUROIMMUNOLOGY AND NEUROMUSCULAR DISEASES UNIT, MILAN, ITALY. – BIOLOGA)
LORENZO MAGGI (FONDAZIONE IRCCS ISTITUTO NEUROLOGICO “”CARLO BESTA””, NEUROIMMUNOLOGY AND NEUROMUSCULAR DISEASES UNIT, MILAN, ITALY. – MEDICO)
FRANCESCO FORTUNATO (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY. – TECNICO DI LABORATORIO)
ANDREA RIGAMONTI (UOC NEUROLOGIA – STROKE UNIT, PRESIDIO “A. MANZONI”, ASST LECCO. – MEDICO)
DARIO RONCHI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY. DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY. – BIOTECNOLOGO)
MONICA SCIACCO (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY. IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE – MEDICO)
GIACOMO PIETRO COMI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY. DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY. – MEDICO)
STEFANIA CORTI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE. DISEASE UNIT, MILAN, ITALY. DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY. – MEDICO)

Presentatore

DANIELA PIGA (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY.)

Modalità

Poster Session

Abstract

“Inclusion body myositis (IBM) is a slowly progressive disorder belonging to the idiopathic inflammatory myopathies and it represents the most common adult-onset acquired myopathy. The main clinical features include proximal or distal muscular asymmetric weakness, with a major involvement of long finger flexors and knee extensors. Main histological findings include the presence of inflammatory infiltrates, rimmed vacuoles and amyloid inclusions. The etiopathogenesis is complex since it likely involves muscle degenerative pathways as well as environmental and genetic factors. In addition, data on the molecular variants associated with hereditary IBM forms (hIBM) and their role in the sporadic presentations are very limited.
We describe a 56 years old Italian patient with a late onset myopathy clinically characterized by atypical weakness distribution, with adipose degeneration of quadriceps and leg muscles, and absence of significant cardiac involvement. Next Generation Sequencing revealed the heterozygous mutation c.76C>T (p.P26S) in the PDZ motif of LDB3/ZASP gene, generally associated to myofibrillar myopathies and cardiomyopathies. This variant met the criteria for pathogenicity and was previously described in two siblings displaying late-onset zaspopathy and clinical severity variability. Therefore this case represents the second report of this pathological variant, that seems to have an incomplete penetrance also in our family. In addition, histological analysis showed typical hIBM-associated skeletal muscle changes with increased expression of Zaspin, Myotilin and Desmin. Ultrastructural findings included typical autophagic vacuoles, core-like alterations and mitochondrial abnormalities in few fibers. Our findings expand our knowledge on the genetic background associated with the inclusion body myositis.”