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.
Savukoski
M
M
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Kestilä
M
M
Williams
R
R
Järvelä
I
I
Sharp
J
J
Harris
J
J
Santavuori
P
P
Gardiner
M
M
Peltonen
L
L
D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002885:Chromosomes, Human, Pair 16; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
D005819:Genetic Markers