Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6

The neuronal ceroid lipofuscinoses (NCL) are heterogeneous neurodegenerative disorders with typical autofluorescence material stored in tissues. Ten clinical NCL forms and eight causative genes are known. Mutations in CLN6 have been reported in roughly 30 patients, mostly in association with the var...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-02, Vol.379 (4), p.892-897
Main Authors: Cannelli, Natalia, Garavaglia, Barbara, Simonati, Alessandro, Aiello, Chiara, Barzaghi, Chiara, Pezzini, Francesco, Cilio, Maria Roberta, Biancheri, Roberta, Morbin, Michela, Bernardina, Bernardo Dalla, Granata, Tiziana, Tessa, Alessandra, Invernizzi, Federica, Pessagno, Alice, Boldrini, Renata, Zibordi, Federica, Grazian, Luisa, Claps, Dianela, Carrozzo, Rosalba, Mole, Sara E., Nardocci, Nardo, Santorelli, Filippo M.
Format: Article
Language:English
Subjects:
Adolescent
Autophagy
Autophagy - genetics
Child
Child, Preschool
CLN6
Cohort Studies
Female
Humans
Lysosomes - ultrastructure
Male
Membrane Proteins - genetics
Mutation
Mutation scanning
Neuronal Ceroid-Lipofuscinoses - genetics
Neuronal Ceroid-Lipofuscinoses - pathology
v-LINCL
Young Adult
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Summary:The neuronal ceroid lipofuscinoses (NCL) are heterogeneous neurodegenerative disorders with typical autofluorescence material stored in tissues. Ten clinical NCL forms and eight causative genes are known. Mutations in CLN6 have been reported in roughly 30 patients, mostly in association with the variant late-infantile NCL (v-LINCL) phenotype. We screened CLN6 in 30 children from a cohort of 53 v-LINCL cases and revised their clinical and ultrastructural features. We detected 11 mutations, eight of which are novel, all predicting a direct impairing of the putative gene function. No clear-cut genotype–phenotype correlations were observed, with inter- and intra-familial variability evident for few recurrent mutations. Ultrastructural findings were suggestive of an impaired regulation of the autophagic vacuoles turnover. While expanding the array of CLN6 mutations, we showed that more than half of our v-LINCL cases lack a DNA confirmation and further molecular etiologies are to be searched.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.12.159