Autophagic vacuolar myopathy is a common feature in CLN3 disease

TY - JOUR

T1 - Autophagic vacuolar myopathy is a common feature in CLN3 disease

AU - Radke, J

AU - Koll, Randi

AU - Gill, Esther

AU - Wiese, L

AU - Schulz, Angela

AU - Kohlschütter, Alfried

AU - Schuelke, Markus

AU - Hagel, Christian

AU - Stenzel, Werner

AU - Goebel, HH

PY - 2018/9/6

Y1 - 2018/9/6

N2 - 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.

AB - 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.

UR - https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.662

U2 - 10.1002/acn3.662

DO - 10.1002/acn3.662

M3 - SCORING: Journal article

C2 - 30480032

VL - 5

SP - 1385

EP - 1393

JO - ANN CLIN TRANSL NEUR

JF - ANN CLIN TRANSL NEUR

SN - 2328-9503

IS - 11

ER -