Figure 1

Heterozygous missense variants in SLC6A9 leading to AIS.

(A) Pedigree of 5 AIS families with dominant inheritance. Squares and circles denote male and female family members, respectively. Filled and open symbols represent affected and unaffected family members, respectively. Individuals marked with numbers indicate the family members recruited in this study. Question marks and diagonal slashes indicate unavailable and deceased members, respectively. The term +/+ denotes WT, and +/R662W or +/Y206F denotes heterozygous variant of SLC6A9. Arrows indicate the probands. (B) Spinal radiographs of the probands of family 1-5. (C) Workflow for the identification of SLC6A9 variants in the multicenter AIS cohort. The number of families and sporadic patients enrolled from each involved hospital is indicated, and the identified SLC6A9 variants are highlighted in the oblique boxes. (D) Membrane topological features of GLYT1. Positions of the identified variants are indicated in the diagram. TM, transmembrane; IL, intracellular loop; EL, extracellular loop. N and C indicate the N- and C-termini of GLYT1, respectively. (E) Evolutionary conservation of altered GLYT1 amino acids associated with AIS. Each variant is shown on the top.