Abstract
Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive neurodegenerative disorders typically characterized by the accumulation of autofluorescent material in tissues. On the basis of clinical features, age at onset, and molecular genetic defects, it is possible to distinguish at least nine forms. The CLN8 form was first described in Finland, where all the patients are homozygous for a p.Arg24Gly mutation in CLN8. More recently, it has been found that a subset of a Turkish variant of late infantile NCL (v-LINCL) is also associated with CLN8 mutations. To identify the molecular defect in Italian patients with v-LINCL, the CLN8 gene was directly sequenced in 10 patients. Controls were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Five fluorescent-labeled microsatellite markers covering 1 cM around the gene were used for haplotype analysis. In three Italian v-LINCL patients, identified in a small area in southern Italy, we detected four new mutations in CLN8: c.66delG (p.Gly22fs), c.88G>C (p.Ala30Pro), c.473A>G (p.Tyr158Cys), and c.581A>G (p.Gln194Arg). The single-base deletion was found in two unrelated patients. The novel missense mutations were not identified in ethnically matched control chromosomes. Our findings expand the number of CLN8 variants and corroborate the notion that CLN8 patients are not confined to the Finnish population.
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Acknowledgements
The authors acknowledge the contribution of Mrs. C.J. Wrenn in editing and revising the manuscript. The skillful technical assistance with electron microscopy of Mrs. Floriana Gismondi is also appreciated. Research in our laboratories is supported by grants from MIUR (Cofinanziamento 2003), the Italian Superior Health Institute (FMS), and the Italian Ministry of Health (Ricerca corrente, strategica, finalizzata 2003, grant no. 132/03 to F.Z.). FMS and NC thank the families for their active participation in this project.
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Table 1
Oligonucleotide primers used to amplify the coding sequence of CLN8 (NT_023736.16) (PDF 53 kb)
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Cannelli, N., Cassandrini, D., Bertini, E. et al. Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis: another genetic hit in the Mediterranean. Neurogenetics 7, 111–117 (2006). https://doi.org/10.1007/s10048-005-0024-y
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DOI: https://doi.org/10.1007/s10048-005-0024-y