Gene symbol: CLN5. Disease: Neuronal Ceroid Lipofuscinosis, finnish variant.

Universidad Nacional de Córdoba, Secretaría de Ciencia y Técnica-SECYT, Centro de Estudio de las MetabolopatíasCongénitas (CEMECO), Hospital de Niños, Ferroviarios, 1250, X5014AKN, Córdoba, Argentinia.
Human Genetics (Impact Factor: 4.52). 06/2008; 123(5):552.
Source: PubMed
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    ABSTRACT: The neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative disorders. Most are autosomal recessively inherited. Clinical features include a variable age of onset, motor and mental decline, epilepsy, visual loss, and premature death. Mutations in eight genes (PPT1/CLN1, TPP1/CLN2, CLN3, CLN5, CLN6, MFSD8/CLN7, CLN8) have been identified and several more are predicted to exist, including two provisionally named CLN4 and CLN9. Despite excessive in vitro and in vivo studies, the precise functions of the NCL proteins and the disease mechanisms remain elusive. To date 365 NCL-causing mutations are known, with 91 novel disease-causing mutations reported. These are reviewed with an emphasis on their complex correlation to phenotypes. Different mutations within the NCL spectrum can cause variable disease severity. The NCLs exemplify both phenotypic convergence or mimicry and phenotypic divergence. For example, mutations in CLN5, CLN6, MFSD8, or CLN8 can underlie the clinically similar late infantile variant NCL disease. Phenotypic divergence is exemplified by different CLN8 mutations giving rise to two very different diseases, the mild CLN8 disease, EPMR (progressive epilepsy with mental retardation), and the more severe CLN8 disease, late infantile variant. The increase in the genetic understanding of the NCLs has led to improved diagnostic approaches, and the recent proposal of a new nomenclature.
    Human Mutation 01/2012; 33(1):42-63. DOI:10.1002/humu.21624 · 5.05 Impact Factor
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    ABSTRACT: The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 265 mutations and 38 polymorphisms ( have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.
    Current pharmaceutical biotechnology 06/2011; 12(6):867-83. DOI:10.2174/138920111795542633 · 2.51 Impact Factor


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May 20, 2014