Table 4 Variants identified in genes not obviously related to mitochondrial function 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 (transcript) | Nucleotide and Amino acid change | Clinical significance (met pathogenicity criteria according to ACMG) | Clinical phenotype (MIM#), inheritance | Testing method |
|---|---|---|---|---|---|---|---|
MT-050 | F/<16 | Possible (3) | CACNA1A (NM_001127222.2) | de novo* heterozygous variant: c.4043G>A, p.(Arg1348Gln) | Known pathogenic (PS2, PM1, PP2, PM2, PM5, PP3, PP5) | Developmental and epileptic encephalopathy 42 (617106), AD | Targeted gene NGS |
MT-061 | F/<16 | Possible (3) | DDX3X (NM_001356.5) | de novo* heterozygous variant: c.1629_1630dup, p.(Phe544TyrfsTer8) | Novel pathogenic (PVS1, PM2, PM6) | Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type (300958) | WES |
MT-040 | F/<16 | Probable (6) | TPP1 (NM_000391.4) | homozygous* variant: c.622C>T, p.(Arg208Ter) | Known pathogenic (PVS1, PM2, PP5) | Ceroid lipofuscinosis, neuronal, 2 (204500), AR | WES |
MT-069 | M/<16 | Possible (4) | KIF1A (NM_001244008.2) | de novo* heterozygous variant: c.173C>T, p.(Ser58Leu) | Known pathogenic (PP3, PS2, PM2, PM5, PP2, PP5) | Autosomal dominant non-syndromic intellectual disability (ORPHA:178469), AD | WES |
MT-029 | M/<16 | Probable (7) | YARS1 (NM_003680.4) | compound heterozygous* variants: 1. c.176T>C, p.(Ile59Thr) 2. c.1440del, p.(Glu480AspfsTer32) | 1. Known likely pathogenic (PM3, PM2, PP3, PP5) 2. Novel likely pathogenic (PM3, PM2, PVS1) | Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2 (619418), AR | WES |
MT-073 | M/<16 | Possible (2) | ANO5 (NM_213599.3) | compound heterozygous* variants: 1. c.1407+5G>A, p.(?) 2. c.2137A>G, p.(Thr713Ala) | 1. Known pathogenic (PM2, PM3, PP3, PP5) 2. Known VUS (PM3, PM2) | Muscular dystrophy, limb-girdle, autosomal recessive 12 (611307), AR Miyoshi muscular dystrophy 3 (613319), AR | Targeted gene NGS |
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-054 | M/<16 | Probable (6) | SETD5 (NM_001080517.3) | heterozygous variant: c.2347-2del, p.(?) | Novel likely pathogenic (PVS1, PM2) | Intellectual developmental disorder, autosomal dominant 23 (615761) | WES |