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- W1975349829 endingPage "e26741" @default.
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- W1975349829 abstract "We performed whole-exome sequencing in two autopsy-confirmed cases and an elderly unaffected control from a multigenerational family with autosomal dominant neuronal ceroid lipofuscinosis (ANCL). A novel single-nucleotide variation (c.344T>G) in the DNAJC5 gene was identified. Mutational screening in an independent family with autosomal dominant ANCL found an in-frame single codon deletion (c.346_348 delCTC) resulting in a deletion of p.Leu116del. These variants fulfill all genetic criteria for disease-causing mutations: they are found in unrelated families with the same disease, exhibit complete segregation between the mutation and the disease, and are absent in healthy controls. In addition, the associated amino acid substitutions are located in evolutionarily highly conserved residues and are predicted to functionally affect the encoded protein (CSPα). The mutations are located in a cysteine-string domain, which is required for membrane targeting/binding, palmitoylation, and oligomerization of CSPα. We performed a comprehensive in silico analysis of the functional and structural impact of both mutations on CSPα. We found that these mutations dramatically decrease the affinity of CSPα for the membrane. We did not identify any significant effect on palmitoylation status of CSPα. However, a reduction of CSPα membrane affinity may change its palmitoylation and affect proper intracellular sorting. We confirm that CSPα has a strong intrinsic aggregation propensity; however, it is not modified by the mutations. A complementary disease-network analysis suggests a potential interaction with other NCLs genes/pathways. This is the first replication study of the identification of DNAJC5 as the disease-causing gene for autosomal dominant ANCL. The identification of the novel gene in ANCL will allow us to gain a better understanding of the pathological mechanism of ANCLs and constitutes a great advance toward the development of new molecular diagnostic tests and may lead to the development of potential therapies." @default.
- W1975349829 created "2016-06-24" @default.
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- W1975349829 date "2011-11-04" @default.
- W1975349829 modified "2023-10-16" @default.
- W1975349829 title "Exome-Sequencing Confirms DNAJC5 Mutations as Cause of Adult Neuronal Ceroid-Lipofuscinosis" @default.
- W1975349829 cites W1502795635 @default.
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- W1975349829 cites W1974359647 @default.
- W1975349829 cites W1975304761 @default.
- W1975349829 cites W1975606544 @default.
- W1975349829 cites W1976103641 @default.
- W1975349829 cites W1977246689 @default.
- W1975349829 cites W1978340565 @default.
- W1975349829 cites W1986176147 @default.
- W1975349829 cites W1990473626 @default.
- W1975349829 cites W1992994281 @default.
- W1975349829 cites W1993711225 @default.
- W1975349829 cites W1994089264 @default.
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- W1975349829 cites W2004549388 @default.
- W1975349829 cites W2011445581 @default.
- W1975349829 cites W2022777594 @default.
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- W1975349829 cites W2026907061 @default.
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- W1975349829 cites W2032755318 @default.
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- W1975349829 cites W2038330825 @default.
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- W1975349829 cites W2068244727 @default.
- W1975349829 cites W2077806752 @default.
- W1975349829 cites W2077809468 @default.
- W1975349829 cites W2083045667 @default.
- W1975349829 cites W2085987859 @default.
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- W1975349829 cites W2132726975 @default.
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- W1975349829 cites W2165298990 @default.
- W1975349829 cites W2166427101 @default.
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- W1975349829 doi "https://doi.org/10.1371/journal.pone.0026741" @default.
- W1975349829 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3208569" @default.
- W1975349829 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22073189" @default.
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