Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis

Jouni Vesa, Elina Hellsten, Linda A. Verkruyse, Laura A. Camp, Juhani Rapola, Pirkko Santavuori, Sandra L. Hofmann, Leena Peltonen

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Abstract

NEURONAL ceroid lipofuscinoses (NCL) represent a group of common progressive encephalopathies of children which have a global incidence of 1 in 12,500 (ref. 1). These severe brain diseases are divided into three autosomal recessive subtypes, assigned to different chromosomal loci2-4. The infantile subtype of NCL (INCL), linked to chromosome 1p32, is characterized by early visual loss and rapidly progressing mental deterioration, resulting in a flat electroencephalogram by 3 years of age; death occurs at 8 to 11 years 5, and characteristic storage bodies are found in brain and other tissues at autopsy6. The molecular pathogenesis underlying the selective loss of neurons of neocortical origin has remained unknown. Here we report the identification, by positional candidate methods, of defects in the palmitoyl-protein thioesterase gene in all 42 Finnish INCL patients and several non-Finnish patients. The most common mutation results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain of patients.

Original languageEnglish (US)
Pages (from-to)584-587
Number of pages4
JournalNature
Volume376
Issue number6541
StatePublished - 1995

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Neuronal Ceroid-Lipofuscinoses
Ceroid
Brain Diseases
Mutation
Genes
Brain
Electroencephalography
Chromosomes
Neurons
Peptides
Incidence
Enzymes
Ceroid lipofuscinosis, neuronal 1, infantile
palmitoyl-protein thioesterase

ASJC Scopus subject areas

  • General

Cite this

Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., ... Peltonen, L. (1995). Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature, 376(6541), 584-587.

Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. / Vesa, Jouni; Hellsten, Elina; Verkruyse, Linda A.; Camp, Laura A.; Rapola, Juhani; Santavuori, Pirkko; Hofmann, Sandra L.; Peltonen, Leena.

In: Nature, Vol. 376, No. 6541, 1995, p. 584-587.

Research output: Contribution to journalArticle

Vesa, J, Hellsten, E, Verkruyse, LA, Camp, LA, Rapola, J, Santavuori, P, Hofmann, SL & Peltonen, L 1995, 'Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis', Nature, vol. 376, no. 6541, pp. 584-587.
Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P et al. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature. 1995;376(6541):584-587.
Vesa, Jouni ; Hellsten, Elina ; Verkruyse, Linda A. ; Camp, Laura A. ; Rapola, Juhani ; Santavuori, Pirkko ; Hofmann, Sandra L. ; Peltonen, Leena. / Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. In: Nature. 1995 ; Vol. 376, No. 6541. pp. 584-587.
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