Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.
Animal, Base-Sequence, Chromosome-Mapping, Chromosomes-Human-Pair-15, Costa-Rica, DNA-Mutational-Analysis, Exons, Female, Gene-Deletion, Gene-Frequency, Haplotypes, Human, Male, Membrane-Proteins, Mice, Molecular-Sequence-Data, Mutation, Neuronal-Ceroid-Lipofuscinosis, Pedigree, Polymorphism-(Genetics), RNA-Messenger, Sequence-Alignment, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Venezuela
Am J Hum Genet 2002 Feb; 70(2):324-35.
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.
Gao, H; Boustany, R M.; Espinola, J A.; Antonellis, K A.; Gillis, T; Qin, X; Liu, S; Donahue, L R.; Bronson, R T.; and et, al, " Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse." (2002). Faculty Research 2000 - 2009. 348.