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Table 1 Summary of known neurological diseases caused by short tandem repeat expansions

From: An update on the neurological short tandem repeat expansion disorders and the emergence of long-read sequencing diagnostics

Abbreviated phenotype (MIM number) Gene Mode of inheritance Repeat Motif Location on Gene Pathogenic repeat numbera Chromosome Coordinates (hg38) Clinical phenotype References
C9-FTD
C9-ALS
(#10550)
C9orf72 AD GGGGCC 5’ Region 24–4000 chr9 27573485 27573546 Frontotemporal dementia, amyotrophic lateral sclerosis [32, 47, 65]
CANVAS
(#614575)
RFC1 AR (AAGGG)400–2000
(ACAGG)exp
AAAAG (normal)
Intron 2 400–2000 chr4 39348425 39348483 Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome [11, 28, 138]
DM1
(#160900)
DMPK AD CTG
(Interruptions: CCG)
3’ Region 50–10,000 chr19 45770205 45770266 Myotonic dystrophy 1 [60, 176]
DM2
(#602668)
CNBP (ZNF9) AD CCTG Intron 1 50–11,000 chr3 129172577 129172656 Myotonic dystrophy 2 [176]
DRPLA
(#125370)
ATN1 AD CAG Exon 5 49–93 chr12 6936717 6936775 Dentatorubral-pallidoluysian atrophy [78]
EIEE1/XLID
(#308350)
(#300419)
(#300215)
ARX XL GCC Exon 2 17–27 chrX 25013654 25013697 Clinical spectrum of disorders including developmental and epileptic encephalopathy 1, hydranencephaly with abnormal genitalia, X-linked lissencephaly 2 and X-linked mental retardation 29 [73, 150]
FAME1 (#601068) SAMD12 AD TTTCA
within TTTTA repeat region
Intron 4 105–3680 chr8 118366813 118366918 Familial adult myoclonic epilepsy 1 [22, 68]
FAME2
(#607876)
STARD7 AD ATTTC
within ATTTT repeat region
Intron 1 150–460 chr2 96197067 96197124 Familial adult myoclonic epilepsy 2 [27]
FAME3
(#613608)
MARCHF6 AD TTTCA
within TTTTA repeat region
Intron 1 700–1035 chr5 10356339 10356411 Familial adult myoclonic epilepsy 3 [40]
FAME6
(#618074)
TNRC6A AD TTTCA
within TTTTA repeat region
Intron 1 ?
(only 1 family)
chr16 24613439 24613532 Familial adult myoclonic epilepsy 6 [68]
FAME7
(#618075)
RAPGEF2 AD TTTCA
within TTTTA repeat region
Intron 14 ?
(only 1 family)
chr4 159342527 159342618 Familial adult myoclonic epilepsy 7 [68]
FRAXE
(#309548)
FMR2 (AFF2) XLR CCG 5’ Region  > 200 chrX 148500605 148500753 Mental retardation, X-linked, FRAXE type [53]
FRDA
(#229300)
FXN AR GAA Intron 1 66–1300 chr9 69037275 69037314 Friedreich ataxia [5, 19, 162]
FXS
(#300624)
FXTAS
(#300623)
FMR1 XL CGG 5’ Region 200–3000
55–200
chrX 147911979 147912111 Fragile X syndrome
Fragile X tremor/ataxia syndrome, premature ovarian failure 1
[162]
[56]
HD
(#143100)
HTT AD CAG
(Interruptions: CAA)
Exon 1 36–250 chr4 3074876 3074941 Huntington disease [96, 101]
HDL1
(#603218)
PRNP AD 24-base
octapeptide PHGGGWGQ
Exon 2 8–14 chr20 4699379 4699380 Huntington disease-like 1 [108]
HDL2
(#606438)
JPH3 AD CTG Exon 2A 40–59 chr16 87604283 87604329 Huntington disease-like 2 [62]
HMN VWA1 AR GGCGCGGAGC Exon 1 3 chr1 1435799 1435820 Hereditary axonal motor neuropathy [121]
NIID
(#603472)
NOTCH2NLC AD CGG 5' Region 66–517 chr1 149390803 149390842 Neuronal intranuclear inclusion disease [55, 118, 146]
OPDM1
(#164310)
LRP12 AD CGG 5' Region 90–130 chr8 104588965 104588999 Oculopharyngodistal myopathy [69]
OPDM2
(#618940)
GIPC1 AD CGG 5’ Region 70–164 chr19 14496029 14496104 Oculopharyngodistal myopathy [172]
OPMD
(#164300)
PABPN1 AD GCG Exon 1 7–18 chr14 23321472 23321511 Oculopharyngeal muscular dystrophy [15, 129]
OPML1
(#618637)
NUTM2B-AS1 AD CGG 5' Region 16–160 chr10 79826364 79826403 Oculopharyngeal myopathy with leukoencephalopathy 1 [69]
SBMA
(#313200)
AR XLR CAG Exon 1 38–68 chrX 67545317 67545419 Spinal and bulbar muscular atrophy of Kennedy (Kennedy's disease) [44, 82, 147]
SCA1
(#164400)
ATXN1 AD CAG
(Interruptions: CAT)
Exon 8 39–91 chr6 16327636 16327723 Spinocerebellar ataxia 1 [120, 141]
SCA2
(#183090)
ATXN2 AD CAG
(Interruptions: CAA, CGG, CGC)
Exon 1 33–200
(29–32
increased ALS risk)
chr12 111598950 111599019 Spinocerebellar ataxia 2 [18, 133, 141, 148]
SCA3
(#109150)
ATXN3 AD CAG Exon 10 53–87 chr14 92071011 92071052 Spinocerebellar ataxia 3 [74]
SCA6
(183086)
CACNA1A AD CAG Exon 47 19–33 chr19 13207858 13207897 Spinocerebellar ataxia 6 [141, 181]
SCA7
(#164500)
ATXN7 AD CAG Exon 1 34–460 chr3 63912685 63912716 Spinocerebellar ataxia 7 [18, 30]
SCA8
(#608768)
ATXN8 AD CAG/TAG 3’ UTR 74–1300 chr13 70139383 70139428 Spinocerebellar ataxia 8 [79, 141, 155]
SCA10
(#603516)
ATXN10 AD ATTCT
(Interruptions: ATCCT)
Intron 9 280–4500 chr22 45795355 45795424 Spinocerebellar ataxia 10 [88, 100, 141]
SCA12
(#604326)
PPP2R2B AD CAG 5’ Region 51–78 chr5 146878729 146878758 Spinocerebellar ataxia 12 [63, 94, 141]
SCA17
(#607136)
TBP AD CAG
(Interruptions: CAT, CAA)
Exon 3 43–66 chr6 170561907 170562017 Spinocerebellar ataxia 17, Huntington disease-like 4 [97, 115, 141]
SCA31
(#117210)
BEAN1 AD TGGAA
within TAAAA and TAGAA repeat region
Intron/
Intergenic region
500–760
(> 110 TGGAA repeats)
chr16 66495475 66495509 Spinocerebellar ataxia 31 [134]
SCA36
(#614153)
NOP56 AD GGCCTG Intron 1 650–2500 chr20 2652733 2652775 Spinocerebellar ataxia 36 [77]
SCA37
(#615945)
DAB1 AD ATTTC
within (ATTTT)7–400 repeat region
5’ Region 31–75 chr1 57367044 57367125 Spinocerebellar ataxia 37 [139]
ULD
(#254800)
CSTB AR CCCCGCCCCGCG Upstream
5’ UTR
30–125 chr21 43776444 43776479 Progressive myoclonic epilepsy 1A (Unverricht and Lundborg disease) [87, 91]
  1. ALS, amyotrophic lateral sclerosis; AS, antisense RNA; CANVAS, cerebellar ataxia neuropathy and vestibular areflexia syndrome; DM1; myotonic dystrophy 1; DM2; myotonic dystrophy 2; DRPLA, dentatorubral-pallidoluysian atrophy; EIEE1, early infantile epileptic encephalopathy 1; FAME, familial adult myoclonic epilepsy; FRAXE, fragile-XE syndrome; FRDA, Friedreich’s ataxia; FTD, frontotemporal dementia; FXS, fragile-X syndrome; FXTAS, fragile-x tremor/ataxia syndrome; HMN, hereditary motor neuropathy; HD, Huntington’s disease; HDL2, Huntington disease-like 2; HDL1, Huntington disease-like 1; LMN, lower motor neuron; NIID, neuronal intranuclear inclusion disease; OPDM, oculopharyngodistal myopathy; OPMD, oculopharyngeal muscular dystrophy; OPML, oculopharyngeal myopathy with leukoencephalopathy; SBMA, spinal and bulbar muscular atrophy; SCA, spinocerebellar ataxia; ULD, Unverricht-Lundborg disease; UMN, upper motor neuron; XLID, x-linked intellectual disability;
  2. aThese ranges vary between studies and often the upper limit is unknown. It is important to note that these are only potentially pathogenic. There is a small (< 1%) subsection of the healthy control population who have expanded alleles with no clinical manifestations. Similarly, there are alleles lower than the given range who may have intermediate alleles and premutation syndromes