Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.


Journal Article

The CLN6 gene that causes variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), a recessively inherited neurodegenerative disease that features blindness, seizures, and cognitive decline, maps to 15q21-23. We have used multiallele markers spanning this approximately 4-Mb candidate interval to reveal a core haplotype, shared in Costa Rican families with vLINCL but not in a Venezuelan kindred, that highlighted a region likely to contain the CLN6 defect. Systematic comparison of genes from the minimal region uncovered a novel candidate, FLJ20561, that exhibited DNA sequence changes specific to the different disease chromosomes: a G-->T transversion in exon 3, introducing a stop codon on the Costa Rican haplotype, and a codon deletion in exon 5, eliminating a conserved tyrosine residue on the Venezuelan chromosome. Furthermore, sequencing of the murine homologue in the nclf mouse, which manifests recessive NCL-like disease, disclosed a third lesion-an extra base pair in exon 4, producing a frameshift truncation on the nclf chromosome. Thus, the novel approximately 36-kD CLN6-gene product augments an intriguing set of unrelated membrane-spanning proteins, whose deficiency causes NCL in mouse and man.

Full Text

Duke Authors

Cited Authors

  • Gao, H; Boustany, R-MN; Espinola, JA; Cotman, SL; Srinidhi, L; Antonellis, KA; Gillis, T; Qin, X; Liu, S; Donahue, LR; Bronson, RT; Faust, JR; Stout, D; Haines, JL; Lerner, TJ; MacDonald, ME

Published Date

  • February 2002

Published In

Volume / Issue

  • 70 / 2

Start / End Page

  • 324 - 335

PubMed ID

  • 11791207

Pubmed Central ID

  • 11791207

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/338190


  • eng

Conference Location

  • United States