Fig. 1.

Identification of the GLU7ALA (E7A) mutation in UCHL1 in kindred NG 1024. (A) Simplified pedigree is shown; affected subjects are denoted by filled symbols (arrow indicates the index case). (B) Coronal MR images of NG 1024–3 (Right) and a control subject (Left) reveal diffuse cerebral and optic chiasmal atrophy (red arrowhead) in the index case. Cortical atrophy is indicated by cerebral volume loss with increase in the subarachnoid and intersulci spaces over the brain, which are filled with cerebrospinal fluid (black in these images). (C) Axial orbital MR images of a control subject (Left) and NG 1024–3 (Right) show optic nerve (red arrowhead) atrophy. (D) Sagittal MR images of a control subject (Left) and NG 1024–3 (Right) reveal cerebral cortical, cerebellar (red circle), and optic tract (red arrowheads) atrophy. (E) Exome sequencing reveals an A to C change. The WT sequence in blue is shown on top, with the mutant base in red below. There was 35-fold coverage, with all reads revealing the substitution. (F) Sanger sequencing confirms the mutation that results in glutamic acid (E, in blue) to alanine (A, in red) change. The unaffected parents are heterozygous for the variant (Right).