Table 3 Variants identified in mitochondrial disease genes in the patient group
From: Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease
Patient ID | Sex/ age of onset (years) | MDC score | Gene (RefSeq) | Nucleotide and Amino acid change | Clinical significance (met pathogenicity criteria according to ACMG) | Clinical phenotype (MIM#), inheritance | Testing method |
|---|---|---|---|---|---|---|---|
mtDNA variants | |||||||
MT-020 | F/>16 | Definite (10) | MT-TL1 (NC_12920.1) | heteroplasmic variant: m.3243A>G (tRNA Leu) | Known pathogenic (PS3, PM2, PM5, PP3) | MELAS (540000), maternal | mtDNA sequencing |
MT-028 | F/>16 | Probable (5) | MT-TL1 (NC_12920.1) | heteroplasmic variant: m.3243A>G (tRNA Leu) | Known pathogenic (PS3, PM2, PM5, PP3) | MELAS (540000), maternal | mtDNA sequencing |
MT-041 | F/>16 | Definite (12) | MT-TL1 (NC_12920.1) | heteroplasmic variant: m.3243A>G (tRNA Leu) | Known pathogenic (PS3, PM2, PM5, PP3) | MELAS (540000), maternal | mtDNA sequencing |
MT-058 | M/<16 | Probable (6) | MT-ATP6 (NC_12920.1) | heteroplasmic variant: m.8993T>C, p.(Leu156Pro) | Known pathogenic (PP5, PS3, PM5, PP3) | Leigh syndrome (256000), maternal | mtDNA sequencing |
MT-049 | F/<16 | Probable (7) | MT-ATP6 (NC_12920.1) | heteroplasmic variant: m.9185T>C, p.(Leu220Pro) | Known pathogenic (PP5, PS3, PP3) | Leigh syndrome (256000), maternal | mtDNA sequencing |
MT-086 | F/>16 | Probable (6) | MT-TK (NC_12920.1) | heteroplasmic variant: m.8344A>G (tRNA Lys) | Known pathogenic (PP5, PS3, PM2, PP3) | MERRF (545000), maternal | WES |
MT-073 | M/<16 | Possible (2) | MT-ND4 (NC_012920.1) | homoplasmic* variant: m.11778G>A, p.(Arg340His) | Known pathogenic (PP5, PS3, PM5, PP3) | Leber optic atrophy (535000), maternal | mtDNA sequencing |
MT-027 | M/<16 | Probable (7) | 13 genes (NC_12920.1) | de novo* heteroplasmic variant: m.6068_11956del | Novel pathogenic (PVS1, PM2, PM6, PM1) | KSS (530000), sporadic | mtDNA del/dup analysis |
nDNA variants | |||||||
MT-056 | F/<16 | Definite (8) | SURF1 (NM_003172.4) | homozygous* variant: c.845_846del, p.(Ser282CysfsTer9) | Known pathogenic (PVS1, PP5, PM2) | Mitochondrial complex IV deficiency, nuclear type 1 (256000), AR | WES |
MT-024 | F/<16 | Probable (7) | TRMU (NM_018006.5) | homozygous* variant: c.835G>A, p.(Val279Met), | Known likely pathogenic (PP5, PM2, BP1, BP6) | Liver failure, transient infantile (613070), AR | WES |
MT-085 | M/<16 | Probable (6) | PNPLA8 (NM_001256007.3) | compound heterozygous* variants: 1. c.2269del, p.(Thr757GlnfsTer10) 2. c.2275_2276del, p.(Leu759AlafsTer4) | 1. Novel pathogenic (PVS1, PM2, PM3) 2. Known likely pathogenic (PVS1, PM2, PM3, PP5) | Mitochondrial myopathy with lactic acidosis (251950), AR | WES |
Patient with inconclusive diagnosis | |||||||
MT-042 | M/<16 | Definite (8) | RRM2B (NM_015713.5) | heterozygous variant: c.414_415del, p.(Tyr138Ter) | Known likely pathogenic (PVS1, PM2) | Mitochondrial DNA depletion syndrome 8 A (encephalomyopathic type with renal tubulopathy) or 8B (MNGIE type) (612075), AR | Targeted gene NGS |
BTD (NM_001370658.1) | compound heterozygous* variants: 1. c.583C>T, p.(Leu195Phe) 2. c.1270G>C, p.(Asp424His) | 1. Known likely pathogenic (PM1, PP2, PM2, PP3, PM3, PP5) 2. Known pathogenic (PM1, PP2, PP3, PM3, PP5, BA1, BS2) | Partial biotinidase deficiency (253260), AR | Targeted gene NGS | |||