Spinocerebellar ataxias: genetic subtypes

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.

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