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 journalArticle

13 Citations (Scopus)

Abstract

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
Volume262
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Ataxia
Cerebellar Ataxia
Mutation
Genes
Atrophy
Ceroid
Mobility Limitation
Exome
Dysarthria
Inborn Genetic Diseases
Protein Transport
Lysosomes
Computational Biology
Neurodegenerative Diseases
Glaucoma
Siblings
Neuronal 5 Ceroid lipofuscinosis
Brain

Keywords

  • Ceroid lipofuscinosis
  • CLN5
  • Hereditary ataxias
  • SCAR

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations. / Mancini, Cecilia; Nassani, Stefano; Guo, Yiran; Chen, Yulan; Giorgio, Elisa; Brussino, Alessandro; Di Gregorio, Eleonora; Cavalieri, Simona; Lo Buono, Nicola; Funaro, Ada; Pizio, Nicola Renato; Nmezi, Bruce; Kyttala, Aija; Santorelli, Filippo Maria; Padiath, Quasar Salem; Hakonarson, Hakon; Zhang, Hao; Brusco, Alfredo.

In: Journal of Neurology, Vol. 262, No. 1, 01.01.2015, p. 173-178.

Research output: Contribution to journalArticle

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, A 2015, 'Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations', Journal of Neurology, vol. 262, no. 1, pp. 173-178. https://doi.org/10.1007/s00415-014-7553-y
Mancini, Cecilia ; Nassani, Stefano ; Guo, Yiran ; Chen, Yulan ; Giorgio, Elisa ; Brussino, Alessandro ; Di Gregorio, Eleonora ; Cavalieri, Simona ; Lo Buono, Nicola ; Funaro, Ada ; Pizio, Nicola Renato ; Nmezi, Bruce ; Kyttala, Aija ; Santorelli, Filippo Maria ; Padiath, Quasar Salem ; Hakonarson, Hakon ; Zhang, Hao ; Brusco, Alfredo. / Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations. In: Journal of Neurology. 2015 ; Vol. 262, No. 1. pp. 173-178.
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