Abstracts

RATIONALE:_ Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative disorders that presents with progressive myoclonic epilepsy, ataxia, and cognitive decline. Classification of NCL relies mostly on the age of onset of the disease, initial clinical manifestations, and the pattern of abnormal accumulation of an autofluorescent lipopigment in neurons. Recently, defective genes have been mapped and identified for various infantile and juvenile forms of NCL, that are associated with autosomal recessive inheritance. However, gene localisation for adult NCL (CLN4) is still pending. We first set out to determine whether CLN4 maps to a previously identified NCL locus. We present here linkage analysis with markers spanning the CLN2 gene in a large kindred with adult NCL (Kufs' disease). METHODS:_ We performed linkage analysis in a large kindred with Kufs' disease, associated with autosomal dominant transmission and documented granular osmiophilic deposits (GROD) in neurons. We studied 47 individuals from the same family, including 6 affected patients. We used 5 polymorphic markers of (CA)n repeats overlapping the CLN2 locus on chromosome 11p15.5. Two-point linkage analysis was performed using the MLINK program. RESULTS:_ We found a suggestion of linkage with a maximum two-point LOD score of 2.45 at theta=0.015 for marker D11S4124. By haplotype construction and identification of recombination events, we determined that the chromosomal region linked to the disease should be located within a 4 cM interval flanked by D11S2362 and D11S1996. This interval is the same as that previously described for the CLN2 gene, which is responsible for the late-infantile NCL. CONCLUSIONS:_ We found a suggestion of linkage in a large kindred with autosomal dominant Kufs' disease at the CLN2 locus. Screening of this candidate gene for mutations is currently under analysis.