Spinocerebellar ataxias are a group of clinically and genetically heterogeneous disorders. We list below an update on all genetic subtypes, including the most recently identified ones, based on mode of inheritance (Table 1: autosomal dominant; Table 2: autosomal recessive; Table 3: X-linked). Chromosomal locus, gene, mutational spectrum and testing methods are given. Because of significant clinical overlap, multigene and multi-method panel testing is recommeded. To see all our spinocerebellar ataxia panels available for testing click here.
Table 1 – Autosomal dominant spinocerebellar ataxias
Recommended testing | ||||||
Subtype | Locus | Gene | Mutational spectrum | FLA/RPA | Seq | Del/dup |
SCA1 | 6p22.3 | ATXN1 | RE | x | ||
SCA2 | 12q24.12 | ATXN2 | RE | x | ||
SCA3 | 14q24.3-q31 | ATXN3 | RE | x | ||
SCA4 | 16q22.1 | unknown | unknown | |||
SCA5 | 11q13.2 | SPTBN2 | P | x | ||
SCA6 | 19p13.2 | CACNA1A | RE, P | x | x | |
SCA7 | 3p14.1 | ATXN7 | RE | x | ||
SCA8 | 13q21 | ATXN8OS | RE | x | ||
SCA9 | unknown | unknown | unknown | |||
SCA10 | 22q13.31 | ATXN10 | RE | x | ||
SCA11 | 15q15.2 | TTBK2 | P | x | ||
SCA12 | 5q32 | PPP2R2B | RE | x | ||
SCA13 | 19q13.33 | KCNC3 | P | x | ||
SCA14 | 19q13.42 | PRKCG | P | x | ||
SCA15 | 3p26.1 | ITPR1 | D, P | x | x | |
SCA16 | see SCA15 | |||||
SCA17 | 6q27 | TBP | RE | x | ||
SCA18 | 7q22-q32 | unknown | unknown | |||
SCA19 | 1p1.,2 | KCND3 | P | |||
SCA20 | 11q21 | vari | D | x | ||
SCA21 | 1p36.33 | TMEM240 | P | x | ||
SCA22 | see SCA19 | |||||
SCA23 | 20p13 | PDYN | P | x | ||
SCA24 | see SCAR4 | |||||
SCA25 | 2p21-p13 | unknown | unknown | |||
SCA26 | 19p13.3 | ? EEF2 | P | x | ||
SCA27 | 13q33.1 | FGF14 | P | x | ||
SCA28 | 18p11.21 | AFG3L2 | P | x | ||
SCA29 | 3p26.1 | ITPR1 | D, P | x | x | |
SCA30 | 4q34.3-q35.1 | unknown | unknown | |||
SCA31 | 16q21 | BEAN1 | I | x | ||
SCA32 | 7q32-q33 | unknown | unknown | |||
SCA33 | not class. | |||||
SCA34 | 6q14.1 | ELOVL4 | P | x | ||
SCA35 | 20p13 | TGM6 | P | x | ||
SCA36 | 20p13 | NOP56 | RE | x | ||
SCA37 | 1p32 | unkown | unknown | |||
SCA38 | 6p12.1 | ELOVL5 | P | x | ||
SCA39 | not class. | |||||
SCA40 | 14q32.11-q32.12 | ? CCDC88C | P | x | ||
SCA41 | 4q27 | TRPC3 | P | x | ||
SCA42 | 17q21.33 | CACNA1G | P | x | ||
SCA43 | 3q25.2 | ? MME | P | x | ||
SCA44 | 6q24.3 | GRM1 | P | x | ||
SCA45 | 5q33.1 | FAT2 | P | x | ||
SCA46 | 19q13.2 | ? PLD3 | P | x | ||
SCA47 | 1p35.2 | PUM1 | P | x | ||
SCA48 | 16p13.3 | ? STUB1 | P | x |
Legend: RE: repeat expansion; P: punctiform (single nucleotide variations, small indels); D: large deletions or duplications; I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing; Del/dup: large deletions/duplications testing (MLPA/qPCR); the question point (?) indicates that the mutation has been detected in one single family or one single patient, so that the subtype needs to be confirmed.
Tabella 2 – Autosomal recessive spinocerebellar ataxias
Recommended testing | ||||||
Subtype | Locus | Gene | Mutational spectrum | FLA/RPA | Seq | Del/dup |
SCAR1 | 9q34.13 | SETX | P, D | x | x | |
SCAR2 | 9q34.3 | PMPCA | P | x | ||
SCAR3 | 6p23-p21 | unknown | ||||
SCAR4 | 1p36 | unknown | ||||
SCAR5 | 15q25.3 | ZNF592 | P | x | ||
SCAR6 | 20q11-q13 | unkown | ||||
SCAR7 | 11p15.4 | TPP1 | P | x | ||
SCAR8 | 6q25.1-q25.2 | SYNE1 | P | x | ||
SCAR9 | 1q42.13 | ADCK3 | P | x | ||
SCAR10 | 3p22.1 | ANO10 | P | x | ||
SCAR11 | 1q32.2 | SYT14 | P | x | ||
SCAR12 | 16q23.2 | WWOX | P | x | ||
SCAR13 | 6q24.3 | GRM1 | P | x | ||
SCAR14 | 11q13.2 | SPTBN2 | P | x | ||
SCAR15 | 3q29 | ? RUBCN | P | x | ||
SCAR16 | 16p13.3 | STUB1 | P | x | ||
SCAR17 | 10q24.31 | CWF19L1 | P | x | ||
SCAR18 | 4q22.1-q22.2 | GRID2 | P | x | ||
SCAR19 | 1p36.11 | ? SLC9A1 | P | x | ||
SCAR20 | 6q14.3 | SNX14 | P | x | ||
SCAR21 | 11q13.1 | SCYL1 | P | x | ||
SCAR22 | 2q11.2 | VWA3B | P | x | ||
SCAR23 | 6p22.3 | TDP2 | P | x | ||
SCAR24 | 3q22.1 | UBA5 | P | x | ||
SCAR25 | 6q21 | ? ATG5 | P | x | ||
SCAR26 | 19q13.31 | ? XRCC1 | P | x | ||
FRDA | 9q21.11 | FXN | RE, P, D | x | x | x |
VED | 8q12.3 | TTPA | P, D | x | x | |
SCAE | 15q26.1 | POLG | P, D | x | x | |
SCAN1 | 14q32.11 | TDP1 | P | x | ||
SCAN2 | see SCAR1 | |||||
CAHH | 7p22.1 | RNF216 | P | x | ||
EAOH | 9p21.1 | APTX | P, D | x | x | |
IOSCA | 10q24.31 | C10orf2 | P | x | ||
SACS | 13q12.12 | SACS | P, D | x | x |
Legend: RE: repeat expansion; P: punctiform (single nucleotide variations, small indels); D: large deletions or duplications; I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing; Del/dup: large deletions/duplications testing (MLPA/qPCR); the question point (?) indicates that the mutation has been detected in one single family or one single patient, so that the subtype needs to be confirmed.
Table 3 – X-linked spinocerebellar ataxias
Subtype | Locus | Gene | Mutation spectrum | Recommended testing | ||
FLA/RPA | Seq | Del/dup | ||||
SCAX1 | Xp11.21-q21.3 | ATP2B3 | P | x | ||
SCAX2 | unknown | unknown | ||||
SCAX3 | unknown | unknown | ||||
SCAX4 | unknown | unknown | ||||
SCAX5 | Xq25-q27.1 | unknown | ||||
ASAT | Xq13.3 | ABCB7 | P | x | ||
FXTAS | Xq27.3 | FMR1 | RE | x |
Legend: RE: repeat expansion; P: punctiform (single nucleotide variations, small indels); I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing.