Figure 1. .

Overview of the SPG31 locus and identified genetic variation in REEP1. A, Within the minimal chromosomal SPG31 region, we screened several genes by direct sequencing analysis. B, REEP1 consists of seven exons (black boxes) and contains two predicted transmembrane domains (TM1 and TM2) and a “deleted in polyposis” domain (TB2/DP1/HVA22). The 3′ UTR comprises a conserved miRNA target site for miR-140 (MT). C, Sequencing traces of the identified unique mutations in six families with uncomplicated HSP. Sequencing analysis was performed using an ABI3730, following standard procedures. PCR primers are available from the authors on request. D, The miR-140 target site in the 3′ UTR is highly conserved. Two mutations within that site change nucleotides that provide G:U wobble base pairing: c.606+43G→U and c.606+50G→A (gray shading, blue letters, and arrows). E, The mature miR-140 gene is also highly conserved, including the two residues that would bind to the mutated nucleotides in the target site (gray shading and arrows). cen = centromere; tel = telomere.