case_images: PMC8281222_01
case_images: PMC8281222_02
case_images: Brain MRI of patient 3 at the ages of 1 year and 9 months old (A,B) and 3 years and 8 month old (C,D). MRI demonstrated bilateral lesions in the brain stem (red arrowheads), thalamus (white arrowheads), and dentate body of cerebellum (yellow arrowheads), with diffusion limitation in diffusion weighted image. There is no significant improvement during the follow-up period.
case_images: fgene-12-611226-g001.jpg
case_images: PMC8281222_02_fgene-12-611226-g001.jpg
case_images: F1
case_images: Brain MRI demonstrated bilateral lesions in the brain stem, thalamus and dentate body of the cerebellum, with diffusion limitation in diffusion-weighted images (Figure 1).
case_images: Localizations and amino acids conservative analysis of GTPBP3 mutations. (A) Schematic presentation of GTPBP3 gene structure and the locus of identified mutations. Square indicates exons and line indicates introns. (B) Amino acids conservative analysis of the mutations among species.
case_images: fgene-12-611226-g002.jpg
case_images: PMC8281222_02_fgene-12-611226-g002.jpg
case_images: F2
case_images: The encoded amino acid residues of these mutations are all localized between the SH3 domain (101-118) and GTP-binding domain (283-301) of Gtpbp3 protein (Figure 2A). Despite the amino acid variation at position 262 (Glu or Gln) among the six investigated species, both Glu and Gln are hydrophilic residues, which present high structure similarities (Figure 2B).
case_images: The pedigrees and identified GTPBP3 mutations. (A) In family 1, the c.413C > T (p. A138V) mutation was detected in the proband and his father, c.509_510del (p. E170Gfs*42) was detected in the proband and his mother. As shown in the pedigree of the nuclear family, c.509_510del (p. E170Gfs*42) was found in his brother as validated by Sanger sequencing. (B) Mutations identified in family 2 as confirmed by Sanger sequencing. The c.544G > T (p. G182X) mutation was found in the proband and her father, and the c.785A > C (p.Q262P) mutation was found in the proband and her mother. As shown in the pedigree of the nuclear family, there is a history of firstborn spontaneous abortion of the mother at the 7th week of gestation. (C) Mutations found in family 3 as confirmed by Sanger sequencing. The c.785A > C (p.Q262P) was found in the proband and her father, mutation c.424G > A (p.E142K) was found in the proband and her mother. The arrow indicates the proband.
case_images: fgene-12-611226-g003.jpg
case_images: PMC8281222_02_fgene-12-611226-g003.jpg
case_images: F3
case_images: E170Gfs*42), which was inherited from his mother (Figure 3A). Q262P) came from the maternal allele (Figure 3B). E142K) and novel mutation c.785A > C (p.Q262P) in GTPBP3, and the c.785A > C (p.Q262P) was inherited from the paternal allele while the c.424G > A (p.E142K) from the maternal allele (Figure 3C).