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

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.

[1]  G. Sutherland,et al.  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. , 1993, American journal of human genetics.

[2]  A. Bowcock,et al.  Microsatellite polymorphism linkage map of human chromosome 13q. , 1993, Genomics.

[3]  J. Rapola.  Neuronal ceroid-lipofuscinoses in childhood. , 1993, Perspectives in pediatric pathology.

[4]  Eric Lander,et al.  Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland , 1992, Nature Genetics.

[5]  I. Järvelä.  Infantile neuronal ceroid lipofuscinosis (CLN1): linkage disequilibrium in the Finnish population and evidence that variant late infantile form (variant CLN2) represents a nonallelic locus. , 1991, Genomics.

[6]  L. Peltonen,et al.  Infantile form of neuronal ceroid lipofuscinosis (CLN1) maps to the short arm of chromosome 1. , 1991, Genomics.

[7]  L. Peltonen,et al.  Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) gene (CLN3) maps to human chromosome 16. , 1990, Genomics.

[8]  Anthony N. Burkitt,et al.  Computer-Simulation Methods , 1990 .

[9]  Henry A. Erlich,et al.  PCR Technology: Principles and Applications for DNA Amplification , 1989 .

[10]  J. Ott.  Computer-simulation methods in human linkage analysis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Higuchi,et al.  Simple and Rapid Preparation of Samples for PCR , 1989 .

[12]  D. Shibata,et al.  Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction , 1988, The Journal of experimental medicine.

[13]  J. Ott,et al.  Strategies for multilocus linkage analysis in humans. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Sainio,et al.  A Variant of Jansky-Bielschowsky Disease , 1982, Neuropediatrics.

[15]  W. Tackmann,et al.  Evoked potentials in neuronal ceroid lipofuscinosis. , 1979, European neurology.

[16]  F. Andermann,et al.  The ultrastructural characteristics of the abnormal cytosomes in Batten-Kufs' disease. , 1977, Brain : a journal of neurology.

[17]  B. Childs,et al.  Genetic heterogeneity. , 1968, The New England journal of medicine.