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The International
Batten Disease Consortium (1995) demonstrated that the
mutation responsible for 73% of Batten disease chromosomes as identified by the
56 haplotype is a genomic deletion of 1.02 kb, including 217 bp of the open
reading frame (nucleotides 598-814), corresponding to 2 exons. Deletion of these
217 bp of coding sequence produces a frameshift, generating a TAA termination
codon 84 bp downstream of the deletion junction. The predicted translation
product is a truncated protein of 181 amino acids consisting of the first 153
residues of the protein, followed by 28 novel amino acids before the stop codon.
Even more of the patients in Finland
carry the 1.02-kb deletion, namely 90%. Jarvela
et al. (1996) developed a rapid diagnostic solid-phase
minisequencing test to detect this deletion.
This 1-kb deletion in homozygous form
always causes a severe phenotype, including blindness, epilepsy, dementia, and
early death at approximately 24 years of age (Munroe
et al., 1997; Jarvela et al., 1997).
Isolation of a novel gene underlying
Batten disease, CLN3. The International Batten Disease Consortium.
Batten disease (also known as juvenile
neuronal ceroid lipofuscinosis) is a recessively inherited neurodegenerative
disorder of childhood characterized by progressive loss of vision, seizures,
and psychomotor disturbances. The Batten disease gene, CLN3, maps to
chromosome 16p12.1. The so-called 56 chromosome haplotype defined by alleles
at the D16S299 and D16S298 loci is shared by 73% of Batten disease
chromosomes. Exon amplification of a cosmid containing D16S298 has yielded a
candidate gene that is disrupted by a 1 kb genomic deletion in all patients
carrying the 56 chromosome. Two separate deletions and a point mutation
altering a splice site in three unrelated families have confirmed the
candidate as the CLN3 gene. The disease gene encodes a novel 438 amino acid
protein of unknown function.
MeSH Terms:
 | Amino Acid Sequence
| Base Sequence
| Child
| Chromosome Deletion
| Cosmids
| DNA, Complementary/isolation &
purification
| DNA, Complementary/analysis
| Female
| Genetic Screening
| Human
| Molecular Sequence Data
| Mutation/genetics
| Neuronal Ceroid-Lipofuscinosis/genetics*
| Sequence Analysis, DNA
| Support, Non-U.S. Gov't
| Support, U.S. Gov't, Non-P.H.S.
| Support, U.S. Gov't, P.H.S.
| Tumor Cells, Cultured/physiology |
| | | | | | | | | | | | | | | | |
Gene Symbols:
| CLN3 |
Substances:
| DNA, Complementary
| Cosmids |
|
Secondary source id:
| GENBANK/U32680 |
Grant support:
| NS32009/NS/NINDS
| NS30152/NS/NINDS
| NS24279/NS/NINDS |
| |
PMID: 7553855, UI: 96016090
|
