Exome sequencing of the human SFPQ gene (Refseq ID NM_005066) in DNA samples from 151 index familial ALS (fALS) patients revealed two independent sequential missense mutations, N533H (c.1597A>C, we have called hsfpqN) and L534I (c.1600C>A, we have called hsfpqL). The gene discussed is SFPQ; the disease is amyotrophic lateral sclerosis.