Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations

Cecilia Mancini, Stefano Nassani, Yiran Guo, Yulan Chen, Elisa Giorgio, Alessandro Brussino, Eleonora Di Gregorio, Simona Cavalieri, Nicola Lo Buono, Ada Funaro, Nicola Renato Pizio, Bruce Nmezi, Aija Kyttala, Filippo Maria Santorelli, Quasar Salem Padiath, Hakon Hakonarson, Hao Zhang, Alfredo Brusco

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalJournal of Neurology
Issue number1
Publication statusPublished - Jan 1 2015


  • Ceroid lipofuscinosis
  • CLN5
  • Hereditary ataxias
  • SCAR

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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