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Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques (2018-03-07)
Pamela Jarrett, Alexander Easton, Kenneth Rockwood, Sarah Dyack, Alexander McCollum, Victoria Siu, Seyed M Mirsattari, Andreu Massot-Tarrús, M Jill Beis, Nolan D'Souza, Sultan Darvesh
ABSTRACT

Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus. Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) mutation in the DNAJC5 gene. The proband brain had an abundance of neuronal lipofuscin in the cerebral cortex, striatum, amygdala, hippocampus, substantia nigra, and cerebellum. There were no amyloid plaques or neurofibrillary tangles. Immunohistochemistry demonstrated that the cholinergic neurons and cholinergic projection fibers were spared, but there was a profound loss of choline acetyltransferase within the caudate, putamen, and basal forebrain. This suggests a loss of choline acetyltransferase as opposed to a loss of the neurons. This report describes the clinical history of autosomal dominant Kufs disease, the genetic mutation within the DNAJC5 gene, and the neuropathological findings demonstrating depletion of choline acetyltransferase in the brain.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Choline Acetyltransferase Antibody, Chemicon®, from goat
Sigma-Aldrich
Anti-Acetylcholinesterase Antibody, clone AE-1, clone AE-1, Chemicon®, from mouse