Spinocerebellar ataxia (SCA) is one of the most heterogenous
genetic disorders known to date. Mutations in different genes can cause the
disease (through autosomal dominant, autosomal recessive or X-linked inheritance).
Several type of mutations are described and different analytical approaches are
therefore required for the test. Here below we present an updated list of all
genetic subtypes known to date, divided by inheritance. For details about the
method required for the analysis of each SCA subtype, please read here.
Table 1 - AUTOSOMAL DOMINANT
SPINOCEREBELLAR ATAXIA
Subtype
|
Chromsomal
Location
|
Gene
|
Mutational
spectrum
|
Required
analysis
|
||
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
|
1p21-q21
|
unknown
|
unknown
|
|||
SCA20
|
11q21
|
unknown
|
D
|
x
|
||
SCA21
|
7p21.3-p15.1
|
unknown
|
unknown
|
|||
SCA22
|
see SCA19
|
|||||
SCA23
|
20p13
|
PDYN
|
P
|
x
|
||
SCA24
|
see SCAR4
|
|||||
SCA25
|
2p21-p13
|
unknown
|
unknown
|
|||
SCA26
|
19p13.3
|
unknown
|
unknown
|
|||
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
|
|||
SCA32
|
7q32-q33
|
unknown
|
unknown
|
|||
SCA33
|
not classified
|
|||||
SCA34
|
6p12.3-q16.2
|
unknown
|
unknown
|
|||
SCA35
|
20p13
|
TGM6
|
P
|
x
|
||
SCA36
|
20p13
|
NOP56
|
RE
|
x
|
||
Legend: RE: repeat expansion; P: point mutation or small deletion/duplication/insertion; D: large deletion/duplication; I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing; Del/dup: deletion/duplication testing (MLPA/qPCR).
Table 2 - AUTOSOMAL RECESSIVE
SPINOCEREBELLAR ATAXIA
Subtype
|
Chromsomal
Location
|
Gene
|
Mutational
spectrum
|
Required
analysis
|
||
FLA/RPA
|
Seq
|
Del/dup
|
||||
SCAR1
|
9q34.13
|
SETX
|
P, D
|
x
|
x
|
|
SCAR2
|
9q34-qter
|
unknown
|
||||
SCAR3
|
6p23-p21
|
unknown
|
||||
SCAR4
|
1p36
|
unknown
|
||||
SCAR5
|
15q25.3
|
ZNF592
|
P
|
x
|
||
SCAR6
|
20q11-q13
|
unknown
|
||||
SCAR7
|
11p15
|
unknown
|
||||
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
|
16q21-q23
|
unknown
|
x
|
|||
SCAR13
|
6q24.3
|
GRM1
|
P
|
x
|
||
SCAR14
|
11q13.2
|
SPTBN2
|
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: point mutation or small deletion/duplication/insertion; D: large deletion/duplication; I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing; Del/dup: deletion/duplication testing (MLPA/qPCR).
Table 3 – X-LINKED
SPINOCEREBELLAR ATAXIA
Subtype
|
Chromsomal
Location
|
Gene
|
Mutational
spectrum
|
Required
analysis
|
||
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: point mutation or small deletion/duplication/insertion; D: large deletion/duplication; I: large insertion; FLA/RPA: fragment length analysis/repeat primed assay; Seq: sequencing; Del/dup: deletion/duplication testing (MLPA/qPCR).
Reference: www.omim.org
