Molecular screening of Batten disease: identification of a missense mutation (E295K) in the CLN3 gene

Hum Genet. 1998 Jan;102(1):57-62. doi: 10.1007/s004390050654.

Abstract

Batten disease, the juvenile form of neuronal ceroid lipofuscinosis, is a prevalent neuron degenerative disorder of childhood. A 1.02-kb genomic deletion in the Batten disease gene CLN3 has been determined to be a common mutation. We developed a PCR method to screen for this deletion and tested 43 Batten disease probands. We found 36% (31/86) of Batten disease chromosomes did not carry the 1.02-kb deletion. Of the three heterozygotes for the 1.02-kb deletion, a novel G-to-A missense mutation at nucleotide 1020 of the CLN3 cDNA sequence was found on two of the non-1.02-kb deletion chromosomes. The missense mutation resulted in a substitution of glutamic acid (E) by lysine (K) at position 295 (E295 K). The E295 K mutation causes a change in predicted local protein conformation. This glutamic acid is a highly conserved acidic amino acid, being present in human, mouse, dog and yeast, which suggests it may play an important role in the function of the Batten disease protein.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Animals
  • Dogs
  • Gene Deletion
  • Genetic Testing*
  • Glutamic Acid / genetics
  • Humans
  • Lysine / genetics
  • Membrane Glycoproteins*
  • Mice
  • Molecular Chaperones*
  • Molecular Sequence Data
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Proteins / genetics*

Substances

  • CLN3 protein, human
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Proteins
  • Glutamic Acid
  • Lysine