Illustrative cases. (A) Integrative Genomics Viewer (IGV) showing aligned sequence reads for proband and unaffected mother at the SPG11 locus. An 8.3 kb deletion is carried by the proband and mother, point mutation is carried only by the proband (red circle). (B–D) Clinical images of the proband. (E) Sagittal MRI midline slice showing corpus callosum atrophy. (F) IGV showing loss of read depth in intron 2 of RFC1 (red circle). Reads with red outline (black arrow) indicated an unmatched read-pair suggestive of an expansion. (G and H) Clinical images of the asymptomatic mother easily walking and standing on heels. (I and J) Wasting of distal upper and lower limbs in the proband. (K) IGV showing a variant in ITPR3 present in the proband and mother, but absent in the father (green arrow).