Z-band alternatively spliced PDZ-motif protein (ZASP) is a sarcomeric component expressed both in cardiac and skeletal muscles. Mutations in the LDB3/ZASP gene cause cardiomyopathy and myofibrillar myopathy. We describe a c.76C>T / p.[Pro26Ser] mutation in the PDZ motif of LDB3/ZASP in two siblings exhibiting late-onset myopathy with axial, proximal and distal muscles involvement and marked variability in clinical severity in the absence of a significant family history for neuromuscular disorders. Notably, we identified involvement of the psoas muscle on MRI and muscle CT, a feature not previously documented. Proband's muscle biopsy showed an increase of ZASP expression by western blotting. Muscle fibres morphological features included peculiar sarcolemmal invaginations, pathological aggregates positive to ZASP, ubiquitin, p62 and LC3 antibodies, and the accumulation of autophagic vacuoles, suggesting that protein aggregate formation and autophagy are involved in this additional case of zaspopathy.

Protein aggregates and autophagy involvement in a family with a mutation in Z-band alternatively spliced PDZ-motif protein / Cassandrini D.; Merlini L.; Pilla F.; Cenni V.; Santi S.; Faldini C.; Santorelli F.M.; Sabatelli P.. - In: NEUROMUSCULAR DISORDERS. - ISSN 0960-8966. - ELETTRONICO. - 31:1(2021), pp. 44-51. [10.1016/j.nmd.2020.11.008]

Protein aggregates and autophagy involvement in a family with a mutation in Z-band alternatively spliced PDZ-motif protein

Merlini L.;Pilla F.;Cenni V.;Santi S.;Faldini C.;
2021

Abstract

Z-band alternatively spliced PDZ-motif protein (ZASP) is a sarcomeric component expressed both in cardiac and skeletal muscles. Mutations in the LDB3/ZASP gene cause cardiomyopathy and myofibrillar myopathy. We describe a c.76C>T / p.[Pro26Ser] mutation in the PDZ motif of LDB3/ZASP in two siblings exhibiting late-onset myopathy with axial, proximal and distal muscles involvement and marked variability in clinical severity in the absence of a significant family history for neuromuscular disorders. Notably, we identified involvement of the psoas muscle on MRI and muscle CT, a feature not previously documented. Proband's muscle biopsy showed an increase of ZASP expression by western blotting. Muscle fibres morphological features included peculiar sarcolemmal invaginations, pathological aggregates positive to ZASP, ubiquitin, p62 and LC3 antibodies, and the accumulation of autophagic vacuoles, suggesting that protein aggregate formation and autophagy are involved in this additional case of zaspopathy.
2021
Protein aggregates and autophagy involvement in a family with a mutation in Z-band alternatively spliced PDZ-motif protein / Cassandrini D.; Merlini L.; Pilla F.; Cenni V.; Santi S.; Faldini C.; Santorelli F.M.; Sabatelli P.. - In: NEUROMUSCULAR DISORDERS. - ISSN 0960-8966. - ELETTRONICO. - 31:1(2021), pp. 44-51. [10.1016/j.nmd.2020.11.008]
Cassandrini D.; Merlini L.; Pilla F.; Cenni V.; Santi S.; Faldini C.; Santorelli F.M.; Sabatelli P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/807371
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