Table 1. Mutations in mitoribosome elements and human disease.
AD, Alzheimer’s disease. AMDF, Ataxia, myoclonus and deafness. CPEO, chronic progressive external ophthalmoplegia. LVNC, left ventricular noncompaction. MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. MERRF, myoclonus epilepsy and ragged red muscle fibers. MNGIE, Myo-, neuro-, gastrointestinal encephalopathy. PD, Parkinson’s disease. POAG, Primary open-angle glaucoma. SNP, Single nucleotide polymorphism. For most mutations, only one or a few references were included. A complete set of references can be found in the MITOMAP database.
| Gene | Mutation | Clinical Manifestations | Ref. |
|---|---|---|---|
| Mutations in mitoribosomal RNAs | |||
| 12S rRNA | T669C, A735G, A745G, C792T, A801G, A827G, A839G, A856G, T921C, C960del, C960CC, T961delT+/-C(n)ins, T961G, T961TC, G988A, T990C, T1005C, A1027G, T1095C, A1116G, T1180G, C1192A, C1192T, C1226G, T1291C, C1310T, A1331G, T1349G, A1374G, T1420G, T1452C, A1453G, A1492C, C1494T, A1517C, C1537T, A1544T, A1546T, G1554A, A1555G, T1575G, T1577G | Non-syndromic antibiotic induced hearing loss | [123,200–203] |
| G652del, G653GG, A663G | Atherosclerosis risk | [204–206] | |
| T721C, T850C, T961C | Possibly LVNC associated | [207] | |
| C869T, T1391C, C1556T | Hypertrophic cardiomyopathy | [208] | |
| A750A, A1438A | Schizophrenia associated | [209] | |
| 16S rRNA | T2158C | Reduced risk PD | [210] |
| T2336C | Hypertrophic cardiomyopathy | [133] | |
| T2352C, G2361A, A2755G | Possibly LVNC associated | [207] | |
| C2639A | POAG associated | [211] | |
| T2648C, C2835T | Rett Syndrome | [135,212] | |
| A2706A | Increased risk of type 2 diabetes | [213] | |
| G3010A A3111T |
CVS and migraine Migraine |
[135] | |
| G3090A | Mitochondrial encephalomyopathy | [132] | |
| C3093G | MELAS | [214] | |
| G3196A | AD/PD associated | [215] | |
| MT-TV | G1606A | AMDF | [216] |
| T1607C | Suspected mitochondrial disease | [217] | |
| A1616G, G1642A | MELAS | [218,219] | |
| C1624T | Leigh syndrome | [220] | |
| A1630G | MNGIE | [221] | |
| A1643G | fatal infantile mitochondrial disease | [222] | |
| G1644A | Leigh syndrome, MELAS, hypertrophic cardiomyopathy | [223] | |
| G1644T | Adult-onset Leigh syndrome | [224] | |
| T1659C | Movement disorder | [225] | |
| Mutations in mitoribosomal proteins | |||
| MRPS28 (bS1m) | c.356A>G (p.Lys119Arg) | Intrauterine growth retardation, facial dysmorphism, sensorineural hearing loss, and development delay | [138] |
| MRPS2 (uS2m) | Compound heterozygous c.328C>T (p.Arg110Cys) c.340G>A (p.Asp114Asn) Homozygous c.413G>A (p.Arg138His) |
Sensorineural hearing loss, developmental delay, and hypoglycemia | [141] |
| MRPS6 (bS6m) | SNP (rs9982601) | Increased risk factor for myocardial infarction | [155,156] |
| MRPS7 (uS7m) | Homozygous c.550A>G (p.Met184Val) |
Congenital sensorineural deafness, progressive hepatic and renal failure, and lactic acidemia | [143] |
| MRPS9 (uS9m) | Included in cryptic microdeletion in chromosome band 2q12.1 | Intellectual disability and development delay | [144] |
| MRPS11 (uS11m) | Ankylosing spondylitis | [154] | |
| MRPS14 (uS14m) | Homozygous c.322C>T (p.Arg108Cys) |
Hypertrophic cardiomyopathy with neonatal lactic acidosis, growth retardation, dysmorphic features, and neurological involvement | [158] |
| MRPS16 (bS16m) | Homozygous c.331C>T (p.Arg111*) |
Fatal neonatal lactic acidosis | [72,73] |
| MRPS22 (mS22) | Homozygous c.509G>A (p.Arg170His) |
Cardiomyopathy, renal tubulopathy, antenatal skin oedema, and muscle hypotonia | [146] |
| Homozygous c.644T>C (p.Leu215Pro) |
Cornelia de Lange-like dysmorphic features, encephalocardiomyopathy | [147] | |
| Homozygous c.1032_1035dup (p.Leu346Asnfs*21) |
Fatal lactic acidosis, cardiomyopathy, and brain abnormalities | [148] | |
| Homozygous c.339+5G>A |
Dysmorphism, hypotonia, developmental delay, and Leigh syndrome-like lesions affecting the medulla oblongata and brain stem | [226] | |
| Homozygous c.404G>A (p.Arg135Gln) Homozygous c.605G>A (p.Arg202His) |
Primary ovarian insufficiency | [149] | |
| MRPS23 (mS23) | Homozygous c.119C>G (p.Pro40Arg) |
Hepatic Disease | [153] |
| MRPS25 (mS25) | Homozygous c.215C>T (p.Pro72Leu) |
Mitochondrial encephalomyopathy | [74] |
| MRPS34 (mS34) | Homozygous c.321+1G>T (p.Val100_Gln107del) Homozygous c.322–10G>A (p.Asn108Leufs*12) (p.Asn108Glyfs*50) Compound heterozygous c.37G>A (p.Glu13Lys) c.94C>T (p.Gln32*) |
Leigh syndrome | [151] |
| MRPS39 (mS39) | Compound heterozygous c.415–2A>G c.1747_1748insCT (p.Phe583Serfs*3) |
Leigh syndrome | [139] |
| MRPL3 (uL3m) | Compound heterozygous c.950C>G (p.Pro317Arg)/large deletion |
Hypertrophic cardiomyopathy and psychomotor retardation | [159] |
| MRPL12 (bL12m) | Homozygous c.542C>T (p.Ala181Val) |
neurological deterioration and growth retardation | [164] |
| MRPL24 (uL24m) | Homozygous c.272C>T (p.Leu91Pro) |
Movement disorder and intellectual disability | [140] |
| MRPL44 (mL44) | Homozygous c.467T>G (p.Leu156Arg) Compound heterozygous c.233G>A (p.Arg78Gln) c.467T>G (p.Leu156Arg) |
Infantile-onset hypertrophic cardiomyopathy | [160,161] |