Figure. The 691_692insAG mutation in exon 6 of OPTN in patients with amyotrophic lateral sclerosis (ALS).
(A) A family of Moroccan origin segregating the ALS disease. The father died at age 36 years, probably from ALS. Three sisters, II-1, II-2, and II-3, dark gray circles, had ALS. Sister II-4, light gray circle, developed rapidly progressive presenile dementia with late signs of motor neuron damage; sister II-5, white circle, is healthy. Line across symbols = deceased. (B) Sanger sequencing chromatograms: II-1, II-2, and II-4 are homozygous to the AG insertion, II-5 is heterozygous, as presented in overlapping chromatogram peaks. The AG insertion is marked in the box. Cntrl = control. (C) Fragment analysis of the 4 sisters. II-1, II-2, and II-4 have a single homozygous peak, the mutant allele at 210 bp. II-5 is heterozygous with 2 peaks presented at 208 and 210 bp. Cntrl with a single homozygous peak at 208 bp. (D) Schematic presentation of OPTN protein, its domains, and regions of interactions. CC = coiled-coil domains; Htt = huntingtin; LZ = Leucine zipper domain; UBAN = ubiquitin binding in ABIN and NEMO domain; Z = zinc finger motif. At the bottom, the effect of the AG insertional mutation on the mRNA open reading frame and protein translation is presented. The AG insertion at codon 127 changes 21 amino acids before introducing a premature stop codon.