ClinVar

In affected members of 3 unrelated families with amyotrophic lateral sclerosis (ALS6; 608030), Kwiatkowski et al. (2009) identified a heterozygous 1561C-T transition in exon 15 of the FUS gene, resulting in an arg521-to-cys (R521C) in the C-terminal domain. The mutation was not found in 1,446 control DNA samples.

Vance et al. (2009) identified a heterozygous R521C mutation in 6 affected members of a British family with ALS6 (Ruddy et al., 2003) and in 3 affected members of an additional family with ALS and in 3 index ALS cases.

Corrado et al. (2010) identified a heterozygous R521C mutation in 2 unrelated Italian patients with ALS6. One had a family history of the disorder, and the other had sporadic disease. Onset occurred at age 34 and 54 years, respectively, and both had an unusual phenotype with proximal, mostly symmetric upper limb weakness with neck and axial involvement.

Millecamps et al. (2010) identified heterozygosity for the R521C mutation in 3 of 162 French probands with familial ALS. One patient was also heterozygous for a mutation in the ANG gene (K17I; 105850.0002), which causes ALS9 (611895),

Yan et al. (2010) identified heterozygosity for the R521C mutation in 6 families with ALS6: 4 were Caucasian, 1 was African American, and 1 was Chinese. Five families had classic ALS6. The proband in the remaining family had ALS, her brother had parkinsonism and dementia, and her mother and sister had dementia. These features expanded the phenotype associated with FUS mutations.