TABLE 1.
Repeat expansion diseases, sorted by their proposed pathogenic mechanism.
| Proposed mechanism | Disease | Gene | Localization | Repeat | Normal | Pathogenic | Reference |
|---|---|---|---|---|---|---|---|
| size | size | ||||||
| LOF | BSS | XYLT1 | Promoter | CGG | 9–20 | 120–800 | LaCroix et al. (2019) |
| LOF | FXS | FMR1 | 5′ UTR | CGG | 5–50 | >200 | Verkerk et al. (1991); Oberlé et al. (1991); Fu et al. (1991) |
| LOF | FRAXE | AFF2 | 5′ UTR | CCG | 4–39 | 200–900 | Knight et al. (1993) |
| LOF | EPM1 | CSTB | 5′ UTR | C4GC4GCG | 2–3 | 30–75 | Lalioti et al., 1997 |
| LOF | GDPAG | GLS | 5′ UTR | GCA | 8–16 | 680–1400 | Van Kuilenburg et al. (2019) |
| LOF | FRDA | FXN | Intron | GAA | 5–34 | 65–1300 | Campuzano et al. (1996) |
| LOF | XDP | TAF1 | Intron | C3TCT | absent | 30–55 | Bragg et al. (2017) |
| polyAla | SPD1 | HOXD13 | Exon | GCG | 15 | 24 | Akarsu et al. (1996) |
| polyAla | BCCD | RUNX2 | Exon | GCN | 17 | 27 | Mundlos et al. (1997) |
| polyAla | HFGS | HOXA13 | Exon | GCN | 12–18 | 18–30 | Goodman et al. (2000) |
| polyAla | BPES | FOXL2 | Exon | GCN | 14 | 19–24 | De Baere et al. (2001) |
| polyAla | HPE5 | ZIC2 | Exon | GCN | 15 | 25 | Brown et al. (2001) |
| polyAla | EIEE1 | ARX | Exon | GCN | 12–16 | 20–23 | Stromme et al. (2002) |
| polyAla | MRGH | SOX3 | Exon | GCN | 15 | 26 | Laumonnier et al. (2002) |
| polyAla | CCHS | PHOX2B | Exon | GCN | 20 | 25–29 | Amiel et al. (2003) |
| polyAla | OPMD | PABPN1 | Exon | GCG | 6–10 | 11–18 | Brais et al. (1998) |
| polyQ | SBMA | AR | Exon | CAG | 9–36 | 38–68 | La Spada et al. (1991) |
| polyQ | DRPLA | ATN1 | Exon | CAG | 3–35 | 48–93 | Koide et al. (1994); Nagafuchi et al. (1994) |
| polyQ | HD | HTT | Exon | CAG | 6–35 | 36–200 | Huntington’s Collaborative Group (1993) |
| polyQ | HDL2 | JPH3 AS | Exon | CAG | 6–28 | 41–58 | Margolis et al. (2001) |
| polyQ | SCA1 | ATXN1 | Exon | CAG | 6–38 | 39–88 | Orr et al. (1993) |
| polyQ | SCA2 | ATXN2 | Exon | CAG | 13–31 | 32–500 | Pulst et al. (1996) |
| polyQ | SCA3 | ATXN3 | Exon | CAG | 12–44 | 55–87 | Kawaguchi et al. (1994) |
| polyQ | SCA6 | CACNA1A | Exon | CAG | 4–18 | 20–33 | Zhuchenko et al. (1997) |
| polyQ | SCA7 | ATXN7 | Exon | CAG | 4–33 | 37–460 | Lindblad et al. (1996) |
| polyQ | SCA8 | ATXN8 | Exon | CAG | 15–50 | 74–250 | Koob et al. (1999) |
| polyQ | SCA17 | TBP | Exon | CAG | 25–40 | 43–66 | Koide et al. (1999) |
| ? | SCA12 | PPP2R2B | 5′ UTR | CAG | 4–32 | 43–78 | Holmes et al. (1999) |
| polyGly | FXTAS | FMR1 | 5′ UTR | CGG | 5–50 | 55–200 | Hagerman et al. (2001) |
| polyGly | NIID | NOTCH2NLC | 5′ UTR | CGG | 7–60 | 60–200 | Ishiura et al. (2019); Sone et al. (2019); Tian et al. (2019); Deng et al. (2019) |
| ? | FXPOI | FMR1 | 5′ UTR | CGG | 5–50 | 55–200 | Conway et al. (1998) |
| ? | OPML | LOC642361 | LncRNA | CGG | 3–16 | 50–60 | Ishiura et al. (2019) |
| ? | OPDM1 | LRP12 | 5′ UTR | CGG | 13–45 | 80–130 | Ishiura et al. (2019) |
| ? | OPDM2 | GIPC1 | 5′ UTR | CGG | 12–32 | 70–120 | Deng et al. (2020) |
| ? | OPDM3 | NOTCH2NLC | 5′ UTR | CGG | 7–60 | 60–200 | Yu et al. (2021) |
| RAN | ALS/FTD | C9ORF72 | Intron | G4C2 | 3–25 | >30 | Dejesus-Hernandez et al. (2011); Renton et al. (2011) |
| RAN | SCA36 | NOP56 | Intron | G3C2T | 5–14 | 650–2,500 | Kobayashi et al. (2011) |
| RAN | SCA31 | BEAN1 | Intron | G2A2T | variable | 110–760 | Sato et al. (2009) |
| ? | CANVAS | RFC1 | Intron | G3A2 | variable | 400–2000 | Cortese et al. (2019); Rafehi et al. (2019) |
| RNA | DM1 | DMPK | 3′ UTR | CTG | 5–37 | 50–10,000 | Mahadevan et al. (1992); Brook et al. (1992); Fu et al. (1992) |
| RNA | DM2 | CNBP | Intron | CCTG | 11–30 | 50–11,000 | Liquori et al. (2001) |
| RNA | FECD3 | TCF4 | Intron | CTG | 5–31 | >50 | Mootha et al. (2014) |
| ? | FAME1 | SAMD12 | Intron | TTTCA | absent | 440–3,680 | Ishiura et al. (2018) |
| ? | FAME2 | STARD7 | Intron | TTTCA | absent | >660–730 | Corbett et al. (2019) |
| ? | FAME3 | MARCHF6 | Intron | TTTCA | absent | >660–2,800 | Florian et al. (2019) |
| ? | FAME4 | YEATS2 | Intron | TTTCA | absent | >500 | Yeetong et al. (2019) |
| ? | FAME6 | TNRC6A | Intron | TTTCA | absent | >400 | Ishiura et al. (2018) |
| ? | FAME7 | RAPGEF2 | Intron | TTTCA | absent | >500 | Ishiura et al. (2018) |
| ? | SCA10 | ATXN10 | Intron | TTCTA | 10–32 | 280–4,500 | Matsuura et al. (2000) |
| ? | SCA37 | DAB1 | Intron | TTTCA | absent | 31–75 | Seixas et al. (2017) |
LOF, loss of function mechanism; polyAla, polyalanine; polyGly, polyglycine; polyQ, polyglutamine; RAN, repeat non-ATG, translation; ALS, amyotrophic lateral sclerosis; BCCD, brachydactyly and cleidocranial dysplasia; BPES, blepharophimosis, ptosis and epicanthus inversus; BSS, Baratela-Scott syndrome; CANVAS, cerebellar ataxia, neuropathy and vestibular areflexia syndrome; CCHS, congenital central hypoventilation syndrome; DM1, myotonic dystrophy type 1; DM2, myotonic dystrophy type 2; DRPLA, dentatorubral-pallidoluysian atrophy; EIEE1, early infantile epileptic encephalopathy type 1; EPM1, progressive myoclonus epilepsy type 1; FAME, familial adult myoclonic epilepsy; FECD3, Fuchs endothelial corneal dystrophy type 3; FRAXE, fragile XE, syndrome; FRDA, Friedreich ataxia; FTD, frontotemporal dementia/; FXPOI, Fragile X-associated premature ovarian infertility; FXS, fragile X syndrome; FXTAS, fragile X-associated tremor ataxia syndrome; GDPAG, global developmental delay, progressive ataxia and elevated glutamine; HD, Huntington disease; HDL2, Huntington disease-like 2; HFGS, hand-foot-genital syndrome; HPE5, holoprosencephaly type 5; MRGH, mental retardation with isolated growth hormone deficiency; NIID, neuronal intranuclear inclusion disease; OPDM, oculopharyngodistal myopathy type; OPMD, oculopharyngeal muscular dystrophy; OPML, oculopharyngeal myopathy with leukoencephalopathy; SBMA, spinal and bulbar muscular atrophy; SPD1, synpolydactyly type 1; SCA, spinocerebellar ataxia; XDP, X-linked dystonia parkinsonism.