From: Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity
Case | Gene | Disease (OMIM) | Mode | Nucleotide change a | Protein change | dbSNP rs ID | MAF (%) | HGMD ID | Parental result/patient’s sex | Polyphen2 predictionb |
---|---|---|---|---|---|---|---|---|---|---|
RCC subunit and assembly factor | ||||||||||
 1 | NDUFS2 | Mitochondrial complex 1 deficiency (252010) | AR | NM_004550.4 455_457delCTC | Ser152del | --- | --- | --- | Paternal | --- |
875 T > C | Met292Thr | 150667550 | <0.01 | CM094573 | Maternal | Possibly damaging | ||||
 2 | NDUFAF5 | Mitochondrial complex 1 deficiency (252010) | AR | NM_024120.4 164A > G | Gln55Arg | --- | --- | --- | Maternal | Probably damaging |
 |  |  |  | 327 + 3A > G |  | --- | --- | --- | Paternal |  |
mtDNA synthesis, transcription, translation, mitochondrial biogenesis and dynamic | ||||||||||
 3* | MTFMT | Leigh syndrome (256000) | AR | NM_139242.3 626G > A | Ser209Leu | 201431517 | 0.1 | CS117162 | Paternal | Possibly damaging- |
998G > C | Ser333Ter | --- | --- |  | Maternal | --- | ||||
 4 | TYMP | Mitochondrial DNA depletion syndrome 1 (MNGIE type) (603041) | AR | NM_001953.3 1160G > A homozygote | Gly387Asp | --- | --- | CM055161 | --- | Probably damaging |
Mitochondrial enzymes | ||||||||||
 5* | ETFB | Glutaric acidemia IIB (231680) | AR | NM_001014763.1 235G > A | Val79Ile | 140608276 | 0.4 | --- | Maternal | Benign |
565C > T | Arg189Cys | 147353781 | 0.3 | --- | Paternal | Possibly damaging | ||||
 6 | PANK2 | HARP syndrome (607236) / Neurodegeneration with brain iron accumulation 1 (234200) | AR | NM_153638.2 137A > T | Asp46Val | 148036492 | 0.2 | --- | Maternal | Benign |
1561G > A | Gly521Arg | 137852959 | <0.02 | CM014248 | Paternal | Probably damaging | ||||
 7* | PCK2 | PEPCK deficiency, mitochondrial (261650) | AR | NM_004563.2 731G > A | Arg244Gln | --- | <0.02 | --- | Not in mother; father not sequenced | Possibly damaging |
1756G > A | Gly586Ser | 61737098 | 0.4 | --- | Maternal | Possibly damaging | ||||
 8* | OTC | Ornithine transcarbamylase deficiency (311250) | X-linked | NM_000531.5 298 + 5G > C hemizygote | --- | 72554348 | 0.2 | CS063357 | Male | --- |
Other genes that affect mitochondrial function or that cause similar clinical phenotypes | ||||||||||
9*/13 | SPAST | Spastic paraplegia 4 (182601) | AD | NM_014946.3 1625A > G | Asp542Gly | 142053576 | <0.05 | CM054864 | --- | Benign |
 10 | CLN6 | Ceroid lipofuscinosis (CLN) 6 (601780)/ CLN Kufs type (204300) | AR | NM_017882.2 278 T > C | Thr93Met | 150001589 | <0.04 | CM120905 | Maternal | Probably damaging |
775G > A | Gly259Ser | 150363441 | <0.02 | Paternal | Probably damaging | |||||
 11 | SLC12A3 | Gitelman syndrome (263800) | AR | NM_000339.2 322C > T | Arg108Trp | --- | --- | CM117057 | --- | Possibly damaging |
965C > T | Ala322Val | 142679083 | 0.5 | CM117024 | --- | Benign | ||||
 12* | SLC3A1 | Cystinuria (220100) | AR | NM_000341.3 241C > T | Arg81Cys | 149813423 | <0.02 | CM090053 | Maternal | Benign |
1400 T > C | Met467Thr | 121912691 | 0.4 | CM941280 | Paternal | Benign |