The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment

Paola Lanteri, Irene Meola, Antonio Canosa, Giovanni De Marco, Annarosa Lomartire, Maria Teresa Rinaudo, Emilio Albamonte, Valeria Ada Sansone, Christian Lunetta, Umberto Manera, Rosario Vasta, Cristina Moglia, Andrea Calvo, Paola Origone, Adriano Chiò, Paola Mandich

Research output: Contribution to journalArticlepeer-review

Abstract

We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500–526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2–27, 400–450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.

Original languageEnglish
JournalNeurobiology of Aging
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • FUS gene
  • Juvenile amyotrophic lateral sclerosis
  • Truncated FUS protein expression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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