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Autophagic vacuolar myopathy is a common feature of CLN3 disease

OBJECTIVE: The neuronal ceroid lipofuscinoses (NCL) are genetic degenerative disorders of brain and retina. NCL with juvenile onset (JNCL) is genetically heterogeneous but most frequently caused by mutations of CLN3. Classical juvenile CLN3 includes a rare protracted form, which has previously been...

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Autores principales: Radke, Josefine, Koll, Randi, Gill, Esther, Wiese, Lars, Schulz, Angela, Kohlschütter, Alfried, Schuelke, Markus, Hagel, Christian, Stenzel, Werner, Goebel, Hans H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243389/
https://www.ncbi.nlm.nih.gov/pubmed/30480032
http://dx.doi.org/10.1002/acn3.662
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author Radke, Josefine
Koll, Randi
Gill, Esther
Wiese, Lars
Schulz, Angela
Kohlschütter, Alfried
Schuelke, Markus
Hagel, Christian
Stenzel, Werner
Goebel, Hans H.
author_facet Radke, Josefine
Koll, Randi
Gill, Esther
Wiese, Lars
Schulz, Angela
Kohlschütter, Alfried
Schuelke, Markus
Hagel, Christian
Stenzel, Werner
Goebel, Hans H.
author_sort Radke, Josefine
collection PubMed
description OBJECTIVE: The neuronal ceroid lipofuscinoses (NCL) are genetic degenerative disorders of brain and retina. NCL with juvenile onset (JNCL) is genetically heterogeneous but most frequently caused by mutations of CLN3. Classical juvenile CLN3 includes a rare protracted form, which has previously been linked to autophagic vacuolar myopathy (AVM). Our study investigates the association of AVM with classic, non‐protracted CLN3. METHODS: Evaluation of skeletal muscle biopsies from three, non‐related patients with classic, non‐protracted and one patient with protracted CLN3 disease by histology, immunohistochemistry, electron microscopy, and Sanger sequencing of the coding region of the CLN3 gene. RESULTS: We identified a novel heterozygous CLN3 mutation (c.1056+34C>A) in one of our patients with classic, non‐protracted CLN3 disease. The skeletal muscle of all CLN3 patients was homogeneously affected by an AVM characterized by autophagic vacuoles with sarcolemmal features and characteristic lysosomal pathology. INTERPRETATION: Our observations show that AVM is not an exceptional phenomenon restricted to protracted CLN3 but rather a common feature in CLN3 myopathology. Therefore, CLN3 myopathology should be included in the diagnostic spectrum of autophagic vacuolar myopathies.
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spelling pubmed-62433892018-11-26 Autophagic vacuolar myopathy is a common feature of CLN3 disease Radke, Josefine Koll, Randi Gill, Esther Wiese, Lars Schulz, Angela Kohlschütter, Alfried Schuelke, Markus Hagel, Christian Stenzel, Werner Goebel, Hans H. Ann Clin Transl Neurol Research Articles OBJECTIVE: The neuronal ceroid lipofuscinoses (NCL) are genetic degenerative disorders of brain and retina. NCL with juvenile onset (JNCL) is genetically heterogeneous but most frequently caused by mutations of CLN3. Classical juvenile CLN3 includes a rare protracted form, which has previously been linked to autophagic vacuolar myopathy (AVM). Our study investigates the association of AVM with classic, non‐protracted CLN3. METHODS: Evaluation of skeletal muscle biopsies from three, non‐related patients with classic, non‐protracted and one patient with protracted CLN3 disease by histology, immunohistochemistry, electron microscopy, and Sanger sequencing of the coding region of the CLN3 gene. RESULTS: We identified a novel heterozygous CLN3 mutation (c.1056+34C>A) in one of our patients with classic, non‐protracted CLN3 disease. The skeletal muscle of all CLN3 patients was homogeneously affected by an AVM characterized by autophagic vacuoles with sarcolemmal features and characteristic lysosomal pathology. INTERPRETATION: Our observations show that AVM is not an exceptional phenomenon restricted to protracted CLN3 but rather a common feature in CLN3 myopathology. Therefore, CLN3 myopathology should be included in the diagnostic spectrum of autophagic vacuolar myopathies. John Wiley and Sons Inc. 2018-10-14 /pmc/articles/PMC6243389/ /pubmed/30480032 http://dx.doi.org/10.1002/acn3.662 Text en © 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Radke, Josefine
Koll, Randi
Gill, Esther
Wiese, Lars
Schulz, Angela
Kohlschütter, Alfried
Schuelke, Markus
Hagel, Christian
Stenzel, Werner
Goebel, Hans H.
Autophagic vacuolar myopathy is a common feature of CLN3 disease
title Autophagic vacuolar myopathy is a common feature of CLN3 disease
title_full Autophagic vacuolar myopathy is a common feature of CLN3 disease
title_fullStr Autophagic vacuolar myopathy is a common feature of CLN3 disease
title_full_unstemmed Autophagic vacuolar myopathy is a common feature of CLN3 disease
title_short Autophagic vacuolar myopathy is a common feature of CLN3 disease
title_sort autophagic vacuolar myopathy is a common feature of cln3 disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243389/
https://www.ncbi.nlm.nih.gov/pubmed/30480032
http://dx.doi.org/10.1002/acn3.662
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