title: Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11p15 and 15q21-23.
abstract: The childhood neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative disorders characterised by progressive visual failure, neurodegeneration, epilepsy and the accumulation of an autofluorescent lipopigment in neurones and other cells. Three main subtypes have been identified according to age of onset, clinical features and ultrastructural morphology. These are infantile NCL (INCL; CLN1), classical late infantile NCL (LINCL; CLN2) and juvenile NCL (JNCL; CLN3). Several atypical forms of late infantile NCL (LINCL) have also been described including a Finnish variant LINCL (CLN5). The CLN2 gene has been excluded from the CLN1, CLN3 and CLN5 loci. A genome search was initiated using a homozygosity mapping strategy in five classical LINCL and two variant LINCL consanguineous families. A common region of homozygosity was identified on chromosome 11p15 in two of the classical families. Analysis of a further 33 classical LINCL families supported linkage in this region (Zmax = 3.07 at theta = 0.06 at D11S1338). A common region of homozygosity was also observed on chromosome 15q21-23 in the two variant LINCL families. Extension of the analysis to include a further seven families of identical ultrastructural phenotype established linkage to this region (Zmax = 6.00 at theta = 0.00 at D15S1020).
authors.affiliation: Department of Paediatrics, University College London Medical School, The Rayne Institute, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Sharp
authors.forename: R B
authors.initials: RB
authors.lastname: Wheeler
authors.forename: B D
authors.initials: BD
authors.lastname: Lake
authors.forename: M
authors.initials: M
authors.lastname: Savukoski
authors.forename: I E
authors.initials: IE
authors.lastname: Järvelä
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
authors.forename: R E
authors.initials: RE
authors.lastname: Williams
mesh_terms: D002675:Child, Preschool; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D005819:Genetic Markers; D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human