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 similar to 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.

The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment / P. Lanteri, I. Meola, A. Canosa, G. De Marco, A. Lomartire, M. Rinaudo, E. Albamonte, V. Sansone, C. Lunetta, U. Manera, R. Vasta, C. Moglia, A. Calvo, P. Origone, A. Chio, P. Mandich. - In: NEUROBIOLOGY OF AGING. - ISSN 1558-1497. - 103(2021), pp. 130.e1-130.e7. [10.1016/j.neurobiolaging.2021.01.029]

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

P. Lanteri;G. De Marco;V. Sansone;R. Vasta;
2021

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 similar to 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.
Juvenile amyotrophic lateral sclerosis; FUS gene; Truncated FUS protein expression
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/853335
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