Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1994 Oct;55(4):695–701.

Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses.

M Savukoski 1, M Kestilä 1, R Williams 1, I Järvelä 1, J Sharp 1, J Harris 1, P Santavuori 1, M Gardiner 1, L Peltonen 1
PMCID: PMC1918303  PMID: 7942847

Abstract

We demonstrate here that at least four genetically separate loci are involved in the pathogenesis of human neuronal ceroid lipofuscinoses (NCLs), fatal brain disorders of children. Earlier the assignments of the infantile and juvenile subtypes of NCL to 1p32 and 16p12 had revealed two loci; and here a variant subtype of the late-infantile form of NCL is mapped to a well-defined region on 13q21.1-q32, whereas the clinically similar, classical form of late-infantile NCL was found to represent the fourth, yet-unidentified NCL locus. The linkage disequilibrium was crucial for locus assignment in our highly limited family material, and the data exemplify the significance of this phenomenon in the random mapping of rare human diseases.

Full text

PDF
695

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andermann E., Jacob J. C., Andermann F., Carpenter S., Wolfe L., Berkovic S. F. The Newfoundland aggregate of neuronal ceroid-lipofuscinosis. Am J Med Genet Suppl. 1988;5:111–116. doi: 10.1002/ajmg.1320310615. [DOI] [PubMed] [Google Scholar]
  2. Bowcock A., Osborne-Lawrence S., Barnes R., Chakravarti A., Washington S., Dunn C. Microsatellite polymorphism linkage map of human chromosome 13q. Genomics. 1993 Feb;15(2):376–386. doi: 10.1006/geno.1993.1071. [DOI] [PubMed] [Google Scholar]
  3. Carpenter S., Karpati G., Andermann F., Jacob J. C., Andermann E. The ultrastructural characteristics of the abnormal cytosomes in Batten-Kufs' disease. Brain. 1977 Mar;100(Pt 1):137–156. doi: 10.1093/brain/100.1.137. [DOI] [PubMed] [Google Scholar]
  4. Gardiner M., Sandford A., Deadman M., Poulton J., Cookson W., Reeders S., Jokiaho I., Peltonen L., Eiberg H., Julier C. Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) gene (CLN3) maps to human chromosome 16. Genomics. 1990 Oct;8(2):387–390. doi: 10.1016/0888-7543(90)90297-8. [DOI] [PubMed] [Google Scholar]
  5. Hästbacka J., de la Chapelle A., Kaitila I., Sistonen P., Weaver A., Lander E. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet. 1992 Nov;2(3):204–211. doi: 10.1038/ng1192-204. [DOI] [PubMed] [Google Scholar]
  6. Järvelä I. Infantile neuronal ceroid lipofuscinosis (CLN1): linkage disequilibrium in the Finnish population and evidence that variant late infantile form (variant CLN2) represents a nonallelic locus. Genomics. 1991 Jun;10(2):333–337. doi: 10.1016/0888-7543(91)90316-7. [DOI] [PubMed] [Google Scholar]
  7. Järvelä I., Schleutker J., Haataja L., Santavuori P., Puhakka L., Manninen T., Palotie A., Sandkuijl L. A., Renlund M., White R. Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1. Genomics. 1991 Jan;9(1):170–173. doi: 10.1016/0888-7543(91)90235-7. [DOI] [PubMed] [Google Scholar]
  8. Kimura S., Goebel H. H. Electron microscopic studies on skin and lymphocytes in early juvenile neuronal ceroid-lipofuscinosis. Brain Dev. 1987;9(6):576–580. doi: 10.1016/s0387-7604(87)80088-8. [DOI] [PubMed] [Google Scholar]
  9. Lake B. D., Cavanagh N. P. Early-juvenile Batten's disease--a recognisable sub-group distinct from other forms of Batten's disease. Analysis of 5 patients. J Neurol Sci. 1978 Apr;36(2):265–271. doi: 10.1016/0022-510x(78)90087-4. [DOI] [PubMed] [Google Scholar]
  10. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ott J. Computer-simulation methods in human linkage analysis. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4175–4178. doi: 10.1073/pnas.86.11.4175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Santavuori P. Neuronal ceroid-lipofuscinoses in childhood. Brain Dev. 1988;10(2):80–83. doi: 10.1016/s0387-7604(88)80075-5. [DOI] [PubMed] [Google Scholar]
  14. Santavuori P., Rapola J., Nuutila A., Raininko R., Lappi M., Launes J., Herva R., Sainio K. The spectrum of Jansky-Bielschowsky disease. Neuropediatrics. 1991 May;22(2):92–96. doi: 10.1055/s-2008-1071423. [DOI] [PubMed] [Google Scholar]
  15. Santavuori P., Rapola J., Raininko R., Autti T., Lappi M., Nuutila A., Launes J., Sainio K. Early juvenile neuronal ceroid-lipofuscinosis or variant Jansky-Bielschowsky disease: diagnostic criteria and nomenclature. J Inherit Metab Dis. 1993;16(2):230–232. doi: 10.1007/BF00710251. [DOI] [PubMed] [Google Scholar]
  16. Santavuori P., Rapola J., Sainio K., Raitta C. A variant of Jansky-Bielschowsky disease. Neuropediatrics. 1982 Aug;13(3):135–141. doi: 10.1055/s-2008-1059612. [DOI] [PubMed] [Google Scholar]
  17. Shibata D. K., Arnheim N., Martin W. J. Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction. J Exp Med. 1988 Jan 1;167(1):225–230. doi: 10.1084/jem.167.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tackmann W., Kuhlendahl D. Evoked potentials in neuronal ceroid lipofuscinosis. Eur Neurol. 1979;18(4):234–242. doi: 10.1159/000115082. [DOI] [PubMed] [Google Scholar]
  19. Williams R., Vesa J., Järvelä I., McKay T., Mitchison H., Hellsten E., Thompson A., Callen D., Sutherland G., Luna-Battadano D. Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes. Am J Hum Genet. 1993 Oct;53(4):931–935. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES