Table 2.
Nuclear gene mutations identified in MELAS syndrome subjects
| Gene symbol | Function | In MitoCarta | Transcript change | Protein change | Literature cited | Zygosity | ACMG Classification | In silico analysis# | Patients |
|---|---|---|---|---|---|---|---|---|---|
| POLG | mtDNA replication | Yes | NM_001126131.1(POLG):c.2243G>C | p.(Trp748Ser) | Tzoulis et al., 2006 | Homozygous | Pathogenic (PS1, PM1, PP2, PP3, PP5) | Pathogenic | 2 (P6, P7) |
| NM_001126131.1(POLG):c.3559C>T | p.(Arg1187Trp) | Reichenbach. et al., 2006 | Heterozygous | Uncertain significance (PM1, PP2, PP3) | Pathogenic | 3 (P1, P3, P5) | |||
| DGUOK | dNTP metabolism | Yes | NM_080916.2(DGUOK):c.468del | p.(Phe156Leufs*45) | Present study | Homozygous | Pathogenic (PVS1, PM2, PP3) | Pathogenic | 2 (P10, P11) |
| SUCLG2 | dNTP metabolism | Yes | NM_003848.3(SUCLG2):c.235G>T | p.(Glu79*) | Present study | Heterozygous | Uncertain significance (PM2, PP3) | Pathogenic | 3 (P1, P3, P5) |
| TRNT1 | post-transcriptional modification of tRNAs | Yes | NM_182916.2(TRNT1):c.947_948insG | p.(Glu318Argfs*11) | Present study | Homozygous | Pathogenic (PVS1, PM2, PP3) | Pathogenic | 1 (P1) |
| LOXHD1 | Normal function of hair cells in the inner ear | No |
NM_144612.6(LOXHD1):c.4690C>T NM_144612.6(LOXHD1):c.2054G>A |
p.(Leu1564Phe) p.(Arg685His) | Present study | Compound Heterozygous | Uncertain significance (PM2, PP3) | Pathogenic | 1 (P2) |
|
NM_144612.6(LOXHD1):c.5813G>A NM_144612.6(LOXHD1):c.1191G>T |
p.(Arg1938His) p.(Trp397Cys) | Present study | Compound Heterozygous | Uncertain significance (PM2, PP3) | Pathogenic | 1 (P4) | |||
| KCNQ1 | Potassium channel protein active in heart muscle | No | NM_000218.3(KCNQ1):c.575G>A | p.(Arg192His) | Present study | Heterozygous | Likely pathogenic (PM1, PM2, PP2, PP3) | Pathogenic | 1 (P9) |
| KCNQ2 | Potassium channel protein active in neurons | No | NM_172107.4(KCNQ2):c.598C>A | p.(Leu200Met) | Present study | Heterozygous | Likely pathogenic (PM1, PM2, PM5, PP2, PP3) | Pathogenic | 1 (P9) |
| NEUROD1 | Transcription factor regulates insulin gene expression | No | NM_002500.4(NEUROD1):c.175G>C | p.(Glu59Gln) | Chapla et al., 2015 | Heterozygous | Uncertain significance (PP3) | Pathogenic | 1 (P2) |
| MYH7 | Codes for beta (β)-myosin heavy chain protein contractions of cardiac muscle | No | NM_000257.4(MYH7):c.1013T>C | p.(Val338Ala) | Present study | Heterozygous | Likely pathogenic (PM1, PM2, PP2, PP3) | Pathogenic | 1 (P8) |