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Review
. 2021 Oct 18:12:754045.
doi: 10.3389/fneur.2021.754045. eCollection 2021.

The Genetic Basis of Phenotypic Heterogeneity in the Neuronal Ceroid Lipofuscinoses

Emily Gardner  1 , Sara E Mole  1
Affiliations
Review

The Genetic Basis of Phenotypic Heterogeneity in the Neuronal Ceroid Lipofuscinoses

Emily Gardner et al. Front Neurol. .

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders that affect children and adults. They share some similar clinical features and the accumulation of autofluorescent storage material. Since the discovery of the first causative genes, more than 530 mutations have been identified across 13 genes in cases diagnosed with NCL. These genes encode a variety of proteins whose functions have not been fully defined; most are lysosomal enzymes, or transmembrane proteins of the lysosome or other organelles. Many mutations in these genes are associated with a typical NCL disease phenotype. However, increasing numbers of variant disease phenotypes are being described, affecting age of onset, severity or progression, and including some distinct clinical phenotypes. This data is collated by the NCL Mutation Database which allows analysis from many perspectives. This article will summarise and interpret current knowledge and understanding of their genetic basis and phenotypic heterogeneity.

Keywords: CLN; NCL; batten disease; gene; lysosomal disease; mutation; neuronal ceroid lipofuscinosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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References

    1. Mole SE, Cotman SL. Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta. (2015) 1852:2237–41. 10.1016/j.bbadis.2015.05.011 - DOI - PMC - PubMed
    1. Zeman W, Dyken P. Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic familial idiocy? Pediatrics. (1969) 44:570–83. - PubMed
    1. Noskova L, Stranecky V, Hartmannova H, Pristoupilova A, Baresova V, Ivanek R, et al. . Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am J Hum Genet. (2011) 89:241–52. 10.1016/j.ajhg.2011.07.003 - DOI - PMC - PubMed
    1. 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) 376:584–7. 10.1038/376584a0 - DOI - PubMed
    1. Consortium TIBD. Isolation of a novel gene underlying batten disease, CLN3. Cell. (1995) 82:949–57. 10.1016/0092-8674(95)90274-0 - DOI - PubMed