FUS/TLS gene mutations are the second most frequent cause of familial ALS in the Spanish population

Abstract

Our objective was to investigate the prevalence of FUS/TLS mutations in a Catalan familial ALS cohort undergoing a mutational study for SOD1 in 2006. We screened 25 probands from non-SOD1 families for FUS/TLS mutations. We identified two FALS probands with FUS/TLS mutations. One carried a C-to-T transition at nucleotide position 1561 (c.1561C>T) producing a p.R521C sequence change at protein level. The phenotype was characterized by a young age at onset (38.2 years old), proximal limb girdle weakness, predominant lower motor neuron signs and dropped head. Survival time ranged from 10 to 36 months. Obligate asymptomatic carriers were detected. Our second ALS6 pedigree carried a C-to-T transition at nucleotide position 1528 (c.1528G>A) producing a p.K510E sequence change at protein level. The phenotype was of an early onset (<40 years old), predominant lower motor neuron disease with short survival (nine months). In conclusion, these are the first two FUS/TLS mutations identified in Spain. The prevalence of this form of FALS (8%) is similar to the Dutch and British populations. FUS/TLS mutations are the second most common cause of FALS in our population.

Key words::

• Fused in sarcoma
• FUS/TLS
• R521C
• K510E
• ALS6
• familial amyotrophic lateral sclerosis
• amyotrophic lateral sclerosis
• MIM 608030
• phenotype
• epidemiology

Acknowledgements

The authors are indebted to members of the family under discussion for their cooperation. JG was supported by a Spanish Fondo de Investigaciones Sanitarias grant (FIS 10/01070). MM received grants from the Fundación Ramón Areces and the Fundación Reina Sofia – CIEN.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.