Fig. 2

Genetic analysis of the TUBB8 variant. (A) Family pedigree. Squares denote male family members, circles for female family members, solid symbols for affected family members, and open symbols for unaffected family members. Short double horizontal lines indicate that there were no offspring. The arrow indicates the proband. The I4L variant in TUBB8 was inherited from the father. WT denotes wild type. (B) Sanger sequencing of the proband and her family members. (C) The position of altered alleles is shown on the gene structure of TUBB8, and the corresponding amino acid is indicated on the TUBB8 protein. (D) Conservation analysis of altered amino acids among five primate species. (E) The 3D model of TUBB8 protein and the location of the variant. (F) and (G) showed the protein conformation and hydrogen bond changes of WT (F) and mutant (G). Ile4 can form hydrogen bonds with Val49 in TUBB8 WT protein (F). In I4L mutant protein, the mutant Leu4 cannot form hydrogen bonds with Val49, and formed hydrogen bonds connections with Arg62 (bottom) and Val64 (top)