Autosomal dominant Kufs' disease: a cause of early onset dementia

Josephson, S. Andrew; Schmidt, R. E.; Millsap, P.; McManus, Dennis Q.; Morris, John C.

doi:10.1016/s0022-510x(01)00546-9

Cited by 45 publications

(59 citation statements)

References 14 publications

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“…In humans, CLN4 includes a rare adult-onset form of NCL known as Kufs' disease. Two groups of phenotypes have been recognized, with some cases demonstrating characteristics of both (2,29). Because neither the gene mutation nor the pathological mechanism has been identified in inherited forms of CLN4, the diagnosis is currently based on clinical, histopathological, and ultrastructural data (4).…”

Section: Ast Canine Model Identifies Arsg As a Candidate Gene For Humanmentioning

confidence: 99%

A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Abitbol

Thibaud

Olby

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G ( ARSG ) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.

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Section: Ast Canine Model Identifies Arsg As a Candidate Gene For Humanmentioning

confidence: 99%

A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Abitbol

Thibaud

Olby

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…2D) and extracerebral tissues [32,33]. semi-detailed fashion [34] as well as molecularly undefined adult NCL 328 [34], CLN4 [35][36][37], and CLN13 [38]. They emphasize the almost com-329 plete to rather mild loss of neurons in cerebral and cerebellar cortices, …”

mentioning

confidence: 96%

Human NCL Neuropathology

Radke

Stenzel

Goebel

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

101

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The neuronal ceroid lipofuscinoses (NCL) currently encompass fourteen genetically different forms, CLN1 to CLN14, but are all morphologically marked by loss of nerve cells, particularly in the cerebral and cerebellar cortices, and the cerebral and extracerebral formation of lipopigments. These lipopigments show distinct ultrastructural patterns, i.e., granular, curvilinear/rectilinear and fingerprint profiles. They contain-although to a different degree among the different CLN forms-subunit C of ATP synthase, saposins A and D, and beta-amyloid proteins. Extracerebral pathology, apart from lipopigment formation, which provides diagnostic information, is scant or non-existent. The retina undergoes atrophy in all childhood forms. While many new data and findings have been obtained by immunohistochemistry in mouse and other animal models, similar findings in human NCL are largely missing, thus recommending respective studies of archived brain tissues. The newly described NCL forms, i.e., CLN 10 to CLN 14, also require further studies to provide complete neuropathology. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)".

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“…Kufs disease type A (CLN4A) is inherited in an autosomal recessive manner and presents with progressive myoclonus. Kufs disease type B (CLN4B), which presents with dementia and various motor-system signs, is the only NCL with presumed autosomal dominant inheritance pattern [90][91][92][93][94]. Ultrastructural examination may show GRODs or FPPs.…”

Section: Rakheja and Mj Bennett / Neuronal Ceroid-lipofuscinosesmentioning

confidence: 99%

Neuronal ceroid-lipofuscinoses

Rakheja

Bennett

2018

TRD

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Abstract. The neuronal ceroid-lipofuscinoses (NCLs) are a group of recessively inherited diseases characterized by progressive neuronal loss, accumulation of intracellular lipofuscin-like autofluorescent storage material with distinctive ultrastructural features, and clinical signs and symptoms of progressive neurodegeneration. Initially classified by the age of onset of clinical signs and symptoms as well as the ultrastructural morphology of the storage material, the growing family of NCLs can now also be biologically classified by their underlying genetic defects. For a few NCLs, we now understand the functions of the proteins encoded by the NCL genes, which has enabled refining of the diagnostic algorithms and ignited hopes for finding effective treatments in the future. Ongoing research into understanding the functions of the remainder of the NCL proteins as well as continuing advancements in technology (such as massively-parallel gene sequencing) has and will continue to inform the clinical approach, diagnostic algorithms, and treatment strategies.

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Autosomal dominant Kufs' disease: a cause of early onset dementia

Cited by 45 publications

References 14 publications

A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Human NCL Neuropathology

Neuronal ceroid-lipofuscinoses

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