Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.

TitleAutosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.
Publication TypeJournal Article
Year of Publication2020
AuthorsNaseri N, Sharma M, Velinov M
JournalClin Genet
Date Published2020 Aug 12

The neuronal ceroid lipofuscinoses (NCLs) are at least 13 distinct progressive neurodegenerative disorders unified by the accumulation of lysosomal auto-fluorescent material called lipofuscin. The only form that occurs via autosomal-dominant inheritance exhibits adult onset and is sometimes referred to as Parry type NCL. The manifestations may include behavioral symptoms followed by seizures, ataxia, dementia, and early death. Mutations in the gene DNAJC5 that codes for the presynaptic co-chaperone cysteine string protein-α (CSPα) were recently reported in sporadic adult-onset cases and in families with dominant inheritance. The mutant CSPα protein may lead to disease progression by both loss and gain of function mechanisms. Iron chelation therapy may be considered as a possible pharmaceutical intervention based on our recent mechanism-based proposal of CSPα oligomerization via ectopic Fe-S cluster-binding, summarized in this review.

Alternate JournalClin. Genet.
PubMed ID32783189
Grant List1R01AG052505 / / National Institute for Aging /
1R01NS095988 / / National Institute for Neurological Disorders and Stroke /
NS098623 / / F31 Student Fellowship /