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Abstract #59446 Published in IGR 16-3
Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations
Mancini C; Nassani S; Guo Y; Chen Y; Giorgio E; Brussino A; Di Gregorio E; Cavalieri S; Lo Buono N; Funaro A; Pizio NR; Nmezi B; Kyttala A; Santorelli FM; Padiath QS; Hakonarson H; Zhang H; Brusco AJournal of Neurology 2015; 262: 173-178
Autosomal recessive inherited ataxias are a growing group of genetic disorders. We report two Italian siblings presenting in their mid-50s with difficulty in walking, dysarthria and progressive cognitive decline. Visual loss, ascribed to glaucoma, manifested a few years before the other symptoms. Brain MRI showed severe cerebellar atrophy, prevalent in the vermis, with marked cortical atrophy of both hemispheres. Exome sequencing identified a novel homozygous mutation (c.935G > A;p.Ser312Asn) in the ceroid neuronal lipofuscinosis type 5 gene (CLN5). Bioinformatics predictions and in vitro studies showed that the mutation was deleterious and likely affects ER-lysosome protein trafficking. Our findings support CLN5 hypomorphic mutations cause autosomal recessive cerebellar ataxia, confirming other reports showing CLN mutations are associated with adult-onset neurodegenerative disorders. We suggest CLN genes should be considered in the molecular analyses of patients presenting with adult-onset autosomal recessive cerebellar ataxia.
Department of Medical Sciences, University of Torino, Via Santena 19, 10126, Turin, Italy.
Full articleClassification:
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)