TABLE 2.
Clinical and Genetic Findings in Patients with GTPBP3 Mutations.
| Patient ID | Sex | Ethic origin | Onset age | Presenting symptoms | Plasma lactate | TTE | Brain MRI | Outcomes, follow-up time, cause of death | GTPBP3 mutations | chromosomal position (hg19) | Domain/site |
| Severe form | |||||||||||
| #72425 (Kopajtich et al., 2014) | F | No data | 3.5 months | Poor feeding, failure to thrive, hypoactivity | 23.3 mmol/l | DCM | No data | Died, 8 months, CHF | c.[484G > C; 673G > A; 964G > C], p.[Ala162Pro; Glu225Lys; Ala322Pro] | g.[17449443;1 7449940;1745 0398] | Ala162Pro and Glu225Lys at position between N-terminus and TrmE-type G domain; Ala322Pro at TrmE-type G domain (249–416) |
| #75191 (Kopajtich et al., 2014) | F | No data | Birth | Poor feeding, hypotonic, respiratory failure | 23 mmol/l | HCM | No data | Died, 1 day, asystolia | c.[1009G > C; 1009G > C], p.[Asp337His; Asp337His] | g.[17451887] | Asp337His at TrmE-type G domain (249–416) |
| #76671 (Kopajtich et al., 2014) | M | No data | Birth | Poor feeding, hypotonic, CHF, metabolic acidosis | 5.2 mmol/l | HCM | Bilateral hyperintensities in thalamus | Died, 10 months, CHF | c.[665-2delA; 665-2delA], p.[Ala222Gly; Asp223_Ser270del; Ala222Gly; Asp223_Ser270del] | g.[17449930] | N/A |
| #81471 (Kopajtich et al., 2014) | M | Romanian | 4 weeks | Hypothermia, recurrent apnea metabolic acidosis | 11 mmol/l | HCM | Hyperintensities in subthalamic nuclei | Died, 5 weeks, acidosis | c.[424G > A; 424G > A], p.[Glu142Lys; Glu142Lys] | g.[17449383] | Glu142Lys at GTP-binding protein TrmE N-terminus (35–152) |
| #83904 (Kopajtich et al., 2014) | F | Turkish | 1 week | Cardiogenic shock, metabolic acidosis | 20 mmol/l | DCM | No data | Died, 9 months, CHF | c.[32_33delinsGTG; 32_33delinsGTG], p.[Gln11Argfs*98; Gln11Argfs*98] | g.[17448452_1 7448453] | Gln11Argfs*98 at transit peptide (1–81)/GTP-binding protein TrmE N-terminus (35–152) |
| #83905 (Kopajtich et al., 2014) | F | Turkish | Birth | Cardiogenic shock, metabolic acidosis | No data | DCM | No data | Died, 10 days, CHF | c.[32_33delinsGTG; 32_33delinsGTG], p.[Gln11Argfs*98; Gln11Argfs*98] | g.[17448452_1 7448453] | Gln11Argfs*98 at transit peptide (1–81)/GTP-binding protein TrmE N-terminus (35–152) |
| Our Patient #1 | M | Chinese | 17 h | Hypothermia, poor response, respiratory failure, cardiogenic shock, metabolic acidosis | 26 mmol/l | Normal | No data | Died, 5 days, CHF | c.[413C > T; c.509_510del], p.[Ala138Val; Gln170Glyfs*42] | g.[17449372;17 449468_174494 69delAG] | Ala138Val at GTP-binding protein TrmE N-terminus (35–152); Gln170Glyfs*42 localized between the SH3 domain (101–118) and GTP-binding domain (283–301) |
| Mild form | |||||||||||
| #49665 (Kopajtich et al., 2014) | M | Arab | 10 years | Intellectual disability, fatigability, visual impairment, slight dyspnea with climbing stairs | 3∼7 mmol/l | HCM | Lactate peaks in parietal and precentral cortex | Alive, 14 years | c.[1291dupC; 1375G > A], p.[Pro430Argfs*86; Glu459Lys] | g.[17452324;1 7452408] | C-terminal |
| #36349 (Kopajtich et al., 2014) | M | Arab | No data | Intellectual disability, fatigability, visual impairment, slight dyspnea with climbing stairs | No data | HCM | Lactate peaks in parietal and precentral cortex | Alive, 17 years | c.[1291dupC; 1375G > A], p.[Pro430Argfs*86; Glu459Lys] | g.[17452324;17 452408] | C-terminal |
| #66143 (Kopajtich et al., 2014) | M | Arab | 2 years | Sudden respiratory failure, CHF | No data | HCM | No data | Alive, 5 years | c.[476A > T; 964G > C], p.[Glu159Val; Ala322Pro] | g.[17449435;17 450398] | Glu159Val at position between N-terminus and TrmE-type G domain; Ala322Pro at TrmE-type G domain (Switch II region (302–312, 314–328) |
| #75168 (Kopajtich et al., 2014) | F | Indian | 2 years | Developmental delay, epileptic seizures | >10 mmol/l | No data | Bilateral hyperintensities in thalamus | Alive, 5 years | c.[770C > A; 770C > A], p.[Pro257His; Pro257His] | g.[17450037] | Pro257His at GTP binding region (256–263); Pro257His at TrmE-type G domain (249–416) |
| #82790 (Kopajtich et al., 2014) | F | Japanese | 1 year | Developmental delay, epileptic seizures, hypotonia | 5.7∼6.5 mmol/l | Normal | Bilateral hyperintensities in thalamus | Alive, 2 years | c.[8G > T; 934_957del], p.[Arg3Leu; Gly312_Val319del] | g.[17448428;17 450368_17 450391] | Arg3Leu at transit peptide (1–81); Gly312_Val319del at TrmE-type G domain (249–416); Gly312_Val319del at Switch II region (302–312, 314–328) |
| Patient No. 24 (Elmas et al., 2019) | F | Turkish | 3 weeks | Mental motor retardation, seizure, hearing disability, thrombocytopenia | No data | Normal | Delayed myelination | Alive, 10years | c.[932C > T,932C > T], p.[Pro311Leu, Pro311Leu] | g.[17450270;17 450270] | Pro311Leu at TrmE-type G domain (249–416) |
| Our Patient #2 | F | Chinese | 1 year | Developmental delay, hypotonia | 7.7∼14 mmol/l | No data | Bilateral lesions in brain stem, thalamus and cerebellum | Alive, 3 years | c.[544G > T; c.785A > C], p.[Gly182X; Gln262Pro] | g.[17449503;17 449956] | Gly182X at position between N-terminus and TrmE-type G domain which cause the loss of TrmE-type G domain and C terminal; Gln262Pro at GTP binding region (256–263) |
| Our Patient #3 | F | Chinese | 1 year | Developmental delay, intellectual disability, fatigability, | 4.26∼16 mmol/l | HCM | Bilateral lesions in brain stem, thalamus and cerebellum | Alive, 3 years | c.[424G > A; c.785A > C], p.[Glu142Lys; Gln262Pro] | g.[17449383;17 449956] | Glu142Lys at GTP-binding protein TrmE N-terminus (35–152); Gln262Pro at GTP binding region (256–263) |
CHF, congestive heart failure; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; N/A, not applicable; TTE, transthoracic echocardiography.