Figure 2.

Mutations in the TH gene. A: Schematic drawing of the genomic structure and location of mutations in human TH gene reported by November 2013. Mutations without annotation are from Willemsen et al. (2010), and the mutations in bold are those studied here. Reference sequence: NM_199292.2 (UniGene) transcript variant a (hTH4 with 528 amino acid). ¹[Knappskog et al., ¹⁹⁹⁵; Ludecke et al., ¹⁹⁹⁶], ²[Royo et al., ²⁰⁰⁵], ³[Calvo et al., ²⁰¹⁰], ⁴ [Mak et al., ²⁰¹⁰], ⁵[Stamelou et al., ²⁰¹²], ⁶[Chi et al., ²⁰¹²], ⁷[Giovanniello et al., ²⁰¹²], ⁸[Cai et al., ²⁰¹³]. B: Tetrameric TH including the catalytic and tetramerization domains (left, PDB 1TOH) with one subunit detailed using human TH crystal structure (right, PDB 2XSN). All THD mutations expressed here for the first time are located in the catalytic and tetramerization domain (right amplification), and are colored red, whereas mutations characterized by others [Knappskog et al., ¹⁹⁹⁵; Ludecke et al., ¹⁹⁹⁶; Royo et al., ²⁰⁰⁵; Calvo et al., ²⁰¹⁰] are shown in blue. The model was prepared using the software Accelrys Discovery Studio.