Table 2.
Pathogenic effect of GDAP1 gene mutations.
| GDAP1 Variant (aa Substitution) | Localization | Inheritance of GDAP1 Mutation | Petite | mtDNA Escape | Effect on csg2Δ | Summarized Effect in Yeast | Clinical Phenotype | |
|---|---|---|---|---|---|---|---|---|
| Tm | CaCl2 | |||||||
| GDAP1 | M | _ | 12 | - | + | + | _ | _ |
|
GDAP1 m1 (ΔC-terminus) |
C | AR | 4 | - | - | - | strong | severe |
|
GDAP1 m2 (Gly327Asp) |
C | AR | 5 | moderate | - | - | strong | severe |
|
GDAP1 m3 (Glu218Glu) |
M | AR | 11 | - | - | - | strong/ moderate | moderate to severe |
|
GDAP1 m4 (Glu222Lys) |
M | AR/AD | 9 | minimal | + | + | weak | weak to moderate |
|
GDAP1 m5 (Leu239Phe) |
M | AR | 10 | maximal | -/+ | -/+ | moderate | moderate in homozygote, lack in heterozygote |
|
GDAP1 m6 (His123Arg) |
M | AD | 5 | - | -/+ | -/+ | weak | weak |
|
GDAP1 m7 (Met116Thr) |
M | AR | 5 | - | -/+ | -/+ | weak | moderate in homozygote |
|
GDAP1 m8 (Ala156Gly) |
M | AD | 6 | - | - | -/+ | moderate | moderate in heterozygote |
The summarized results illustrating the pathogenic effect of GDAP1 versions analyzed on selected phenotypes in yeast in comparison to the clinical effect. Localization: C-cytoplasmic, M-mitochondrial; Inheritance AR—autosomal recessive, AD—autosomal dominant; Petite—the results show the percentage of small colonies in the cells expressing GDAP1 variants; mt DNA escape —the effect of the GDAP1 variants expression on a rate of mitochondrial DNA escape reported as maximal, moderate or minimal; effect of GDAP1 variants expression on the csg2Δ mutant ability to grow on media containing tunicamycin (Tm) or calcium chloride (CaCl2) (+) strong, (+/-) moderate, or (-) no effect.