Molecular Genetics of the Neuronal Ceroid Lipofuscinoses

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are a group of clinically and genetically heterogenenous neurodegenerative disorders characterised by the accumulation of autofluorescent storage material in many cell types. Most display autosomal recessive inheritance. More than 400 mutations have been described in 13 genes: PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, GRN, ATP13A2, KCTD7, CTSF and DNAJC5, and none show obvious mutation hotspots. The functions of most of these genes remain elusive. The majority of the genetic defects identified are private, but there are geographically widespread or localised common founder mutations. The NCLs exemplify both phenotypic convergence and divergence, and there can be very wide disease severity caused by mutations in the same gene. Some recently identified mutations are in genes that are associated with other diseases. The recent expansion of knowledge in the genetic understanding of the NCLs is leading to improved diagnostic approaches, and the recent adoption of a new nomenclature.

Key Concepts:

  • More than 400 mutations are known across 13 genes causing disease in families diagnosed with NCL.

  • Most NCLs are autosomal recessive.

  • NCLs are a heterogenous group of disorders with common features of progressive degeneration of the brain, and often the retina, and intracellular storage of material similar to ceroid and lipofuscin.

  • NCLs are monogenic disorders.

  • One type of NCL is autosomal dominant.

  • There remain families diagnosed with NCL in which the genetic cause is not yet determined.

Keywords: Batten; CLN ; neuronal ceroid lipofuscinosis; NCL ; neurodegeneration; paediatric; lysosome; recessive

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Further Reading

Mole SE , Williams RE and Cooper JD (2013) Special issue: molecular basis of NCL. Biochimica et Biophysica Acta 1832: 1793–1794.

Web Links

Mole SE (2013) NCL Resource [Online]. http://www.ucl.ac.uk/ncl

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How to Cite close
Mole, Sara E(Jan 2014) Molecular Genetics of the Neuronal Ceroid Lipofuscinoses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024913]