Refined assignment of the infantile neuronal ceroid-lipofuscinosis (INCL) locus at 1p32 and the current status of prenatal and carrier diagnostics
The refined assignment of the INCL locus and the observed strong linkage disequilibrium with one highly informative tetranucleotide repeat polymorphism at 1p32 has created reliable tools for DNA-based prenatal and carrier diagnosis of INCL in the majority of the families. The observed tendency for homozygosity of one rare allele in Finnish INCL patients suggests a very close physical distance to the INCL gene and provides an excellent starting point for the molecular cloning of the gene. Identification of the gene defect causing this fatal brain disease will reveal the molecular pathogenesis of the disease but also will provide new information of a factor essential for normal postnatal development of cortical neurons.
KeywordsLinkage Disequilibrium Cortical Neuron Molecular Cloning Brain Disease Physical Distance
Unable to display preview. Download preview PDF.
- Botstein D, White R, Skolnick M, Davis RW (1980) Construction of a genetic linkage map using restriction fragment length polymorphisms.Am J Hum Genet 32: 314–331.Google Scholar
- Haltia M, Rapola J, Santavuori P, Keränen A (1973) Infantile type of so-called neuronal ceroid lipofuscinosis. Part 2. Morphological and biochemical studies.J Neurol Sci 18: 269–285.Google Scholar
- Järvelä I (1991) Infantile neuronal ceroid lipofuscinosis (CLN1): Linkage disequilibrium in the Finnish population and evidence that variant late infantile CLN (variant CLN2) represents a non-allelic locus.Genomics 10: 333–337.Google Scholar
- Järvelä I, Rapola J, Peltonen L et al (1991) DNA-based prenatal diagnosis of the infantile form of neuronal ceroid lipofuscinosis (INCL).Prenat Diagn 11: 323–328.Google Scholar
- Mäkelä TP, Hellsten E, Vesa J, Järvelä I, Alitalo K, Peltonen L (1992) An Alu variable polyA repeat upstream from L-myc at 1p32.Hum Mol Genet 1: 217.Google Scholar
- Ott J (1991)Analysis of Human Genetic Linkage. Baltimore: The Johns Hopkins University Press.Google Scholar
- Rapola J, Salonen R, Ammälä P, Santavuori P (1990) Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi.Prenat Diagn 10: 553–559.Google Scholar
- Santavuori P (1988) Neuronal ceroid lipofuscinoses in childhood.Brain Dev 10: 80–83.Google Scholar
- Santavuori P, Haltia M, Rapola J, Raitta C (1974) Infantile type of so-called neuronal ceroid lipofuscinosis.Dev Med Child Neurol 16: 644–653.Google Scholar
- Vesa J, Hellsten E, Mäkelä TP, Järvelä I, Airaksinen T, Santavuori P, Pettonen L (1993) A single PCR marker in strong allelic association with the infantile form of neuronal ceroid lipofuscinosis facilitates reliable prenatal diagnostics and disease carrier identification.Eur J Hum Genet 1: 125–132.Google Scholar