Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

Hdl Handle:
http://hdl.handle.net/10147/230233
Title:
Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.
Authors:
Arsov, Todor; Smith, Katherine R; Damiano, John; Franceschetti, Silvana; Canafoglia, Laura; Bromhead, Catherine J; Andermann, Eva; Vears, Danya F; Cossette, Patrick; Rajagopalan, Sulekha; McDougall, Alan; Sofia, Vito; Farrell, Michael; Aguglia, Umberto; Zini, Andrea; Meletti, Stefano; Morbin, Michela; Mullen, Saul; Andermann, Frederick; Mole, Sara E; Bahlo, Melanie; Berkovic, Samuel F
Affiliation:
Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.
Citation:
Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. 2011, 88 (5):566-73 Am. J. Hum. Genet.
Journal:
American journal of human genetics
Issue Date:
13-May-2011
URI:
http://hdl.handle.net/10147/230233
DOI:
10.1016/j.ajhg.2011.04.004
PubMed ID:
21549341
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146726/pdf/main.pdf
Abstract:
The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Adult; Age of Onset; Biopsy; Dementia; Exons; Female; Genetic Linkage; Genetic Testing; Genotype; Heterozygote; Humans; Male; Membrane Proteins; Middle Aged; Mutation; Neuronal Ceroid-Lipofuscinoses; Pedigree; Polymorphism, Single Nucleotide
ISSN:
1537-6605

Full metadata record

DC FieldValue Language
dc.contributor.authorArsov, Todoren_GB
dc.contributor.authorSmith, Katherine Ren_GB
dc.contributor.authorDamiano, Johnen_GB
dc.contributor.authorFranceschetti, Silvanaen_GB
dc.contributor.authorCanafoglia, Lauraen_GB
dc.contributor.authorBromhead, Catherine Jen_GB
dc.contributor.authorAndermann, Evaen_GB
dc.contributor.authorVears, Danya Fen_GB
dc.contributor.authorCossette, Patricken_GB
dc.contributor.authorRajagopalan, Sulekhaen_GB
dc.contributor.authorMcDougall, Alanen_GB
dc.contributor.authorSofia, Vitoen_GB
dc.contributor.authorFarrell, Michaelen_GB
dc.contributor.authorAguglia, Umbertoen_GB
dc.contributor.authorZini, Andreaen_GB
dc.contributor.authorMeletti, Stefanoen_GB
dc.contributor.authorMorbin, Michelaen_GB
dc.contributor.authorMullen, Saulen_GB
dc.contributor.authorAndermann, Fredericken_GB
dc.contributor.authorMole, Sara Een_GB
dc.contributor.authorBahlo, Melanieen_GB
dc.contributor.authorBerkovic, Samuel Fen_GB
dc.date.accessioned2012-06-22T12:46:36Z-
dc.date.available2012-06-22T12:46:36Z-
dc.date.issued2011-05-13-
dc.identifier.citationKufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. 2011, 88 (5):566-73 Am. J. Hum. Genet.en_GB
dc.identifier.issn1537-6605-
dc.identifier.pmid21549341-
dc.identifier.doi10.1016/j.ajhg.2011.04.004-
dc.identifier.urihttp://hdl.handle.net/10147/230233-
dc.description.abstractThe molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146726/pdf/main.pdfen_GB
dc.rightsArchived with thanks to American journal of human geneticsen_GB
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAge of Onset-
dc.subject.meshBiopsy-
dc.subject.meshDementia-
dc.subject.meshExons-
dc.subject.meshFemale-
dc.subject.meshGenetic Linkage-
dc.subject.meshGenetic Testing-
dc.subject.meshGenotype-
dc.subject.meshHeterozygote-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMembrane Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshMutation-
dc.subject.meshNeuronal Ceroid-Lipofuscinoses-
dc.subject.meshPedigree-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.titleKufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.en_GB
dc.typeArticleen
dc.contributor.departmentEpilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.en_GB
dc.identifier.journalAmerican journal of human geneticsen_GB
dc.description.provinceLeinsteren

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