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Title: Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis

Abstract

The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. 6 refs., 1 fig., 1 tab.

Authors:
; ;  [1]
  1. Rayne Institute, London (United Kingdom) [and others
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
105199
Report Number(s):
CONF-9405333-
Journal ID: AJMGDA; ISSN 0148-7299; TRN: 95:006226-0010
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 57; Journal Issue: 2; Conference: 5. international conference on neuronal ceroid-lipofuscinoses, Staten Island, NY (United States), 19-21 May 1994; Other Information: PBD: 5 Jun 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; NERVOUS SYSTEM DISEASES; HEREDITARY DISEASES; GENES; PATHOGENESIS; HUMAN CHROMOSOME 16; GENETIC MAPPING; HUMAN CHROMOSOME 1; HUMAN CHROMOSOME 13; BIOLOGICAL MARKERS; STATISTICS; GENETICS; RECESSIVE MUTATIONS; POLYMERASE CHAIN REACTION; COMPUTER CODES

Citation Formats

Sharp, J., Wheeler, R.B., and Jaervelae, I.. Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis. United States: N. p., 1995. Web. doi:10.1002/ajmg.1320570249.
Sharp, J., Wheeler, R.B., & Jaervelae, I.. Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis. United States. doi:10.1002/ajmg.1320570249.
Sharp, J., Wheeler, R.B., and Jaervelae, I.. 1995. "Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis". United States. doi:10.1002/ajmg.1320570249.
@article{osti_105199,
title = {Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis},
author = {Sharp, J. and Wheeler, R.B. and Jaervelae, I.},
abstractNote = {The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. 6 refs., 1 fig., 1 tab.},
doi = {10.1002/ajmg.1320570249},
journal = {American Journal of Medical Genetics},
number = 2,
volume = 57,
place = {United States},
year = 1995,
month = 6
}
  • The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. The biochemical basis of these diseases is unknown. Three main childhood forms are recognized: infantile (Santavuori-Haltia disease, CLN1), late infantile (Jansky-Bielschowsky disease, CLN2), and juvenile (Spielmeyer-Vogt-Sjoegren, Batten disease, CLN3). The CLN1 gene has been mapped to chromosome 1p and CLN3 to chromosome 16p by linkage analysis. The gene locus causing the classical late infantile form (CLN2) has not yet been mapped but has been excluded from both CLN1 and CLN3 loci. About 10% of NCLmore » cases have a typical clinical features with most of these resembling the late infantile form. 8 refs., 1 fig., 1 tab.« less
  • Infantile neuronal ceroid lipofuscinosis, INCL, CLN1, is an autosomally inherited progressive neuro-generative disorder. The disease results in the massive death of cortical neurons, suggesting an essential role for the CLN1 gene product in the normal neuronal maturation during the first years of life. Identification of new multiallelic markers has now made possible the construction of a refined genetic map encompassing the CLN1 locus at 1p32. Strong allelic association was detected with a new, highly polymorphic HY-TM1 marker. The authors incorporated this observed linkage disequilibrium into multipoint linkage analysis, which significantly increased the informativeness of the limited family material and facilitatedmore » refined assignment of the CLN1 locus. 23 refs., 2 figs., 4 tabs.« less
  • The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: Infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjoegren-Vogt, or Batten disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). Themore » three childhood subtypes of NCL therefore arise from mutations at distinct loci. 17 refs., 2 figs., 3 tabs.« less
  • The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. The authors have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored bymore » odds of greater than 10[sup 4]:1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct. 23 refs., 3 figs., 2 tabs.« less
  • The loci for juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively. The late-infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci. We have initiated a genome-wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it possible to carry out successful linkage analysis in smallmore » nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18-22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene. 14 refs., 3 tabs.« less