Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6
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- 作者：Natalia Cannelli ; Barbara Garavaglia ; Aless ; ro Simonati ; Chiara Aiello ; Chiara Barzaghi ; Francesco Pezzini ; Maria Roberta Cilio ; Roberta Biancheri ; Michela Morbin ; Bernardo Dalla Bernardina ; Tiziana G
- 关键词：v-LINCL ; CLN6 ; Autophagy ; Mutation scanning
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：20 February 2009
- 年：2009
- 卷：379
- 期：4
- 页码：892-897
- 全文大小：314 K
文摘
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.