ABSTRACT
-
Objective
Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort.
-
Methods
Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control.
-
Results
Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant).
-
Conclusion
Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.
-
Keywords: Sporadic; cerebellar ataxia; spinocerebellar ataxia type 6; heredity
Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, toxic agents, immune-mediated inflammation, vitamin deficiency, superficial siderosis, chronic central nervous system (CNS) infection, multiple system atrophy of cerebellar type (MSA-C), and sporadic cortical cerebellar ataxia (CCA) [
1-
4]. In Asian countries, including Japan, it is recognized that the most common sporadic cerebellar ataxia is MSA-C [
4]. Recently, an autosomal dominant spinocerebellar ataxia (SCA) mutation has been recognized among non-MSA-C sporadic cerebellar ataxia [
5-
7]. Abele et al. [
1] found that 18.8% of 80 patients with adult-onset sporadic cerebellar ataxia carry a disease-causing dominant SCA mutation, comprising seven SCA type 6, five Friedreich’s ataxia, two SCA3, and one SCA2. In Asian countries including China where Friedreich’s ataxia is rare, Wang et al. [
8] found that 17.3% of 237 patients with sporadic cerebellar ataxia carry a disease-causing dominant SCA mutation, which includes 23 SCA3, nine SCA2, six SCA1, and three SCA6 mutations. Because SCA6 seems to have the latest disease onset among all types of SCA [
9], mutations in the gene that causes SCA6 (
CACNA1A) might be found most frequently in patients with sporadic cerebellar ataxia. To confirm this hypothesis, we genetically screened SCA genes in a Japanese single-hospital cohort.
MATERIALS & METHODS
This is a retrospective study. The initial inclusion criteria were any patients with cerebellar ataxia that were referred to our neurology clinic over an 8-year period. All patients were followed for 5 years in order to ascertain the clinical diagnosis. As the initial workup, all patients underwent standard neurological examination, cognitive screening tests comprising the Mini-Mental State Examination (0–30) [
10] and the Frontal Assessment Battery (0–18) [
11], brain imaging comprising magnetic resonance imaging (MRI) and single-photon emission computed tomography using [
99mTc]-labeled L,L-ethyl cysteinate dimer. The exclusion criteria included degenerative neurologic diseases that potentially show cerebellar ataxia (progressive supranuclear palsy, prion disease, etc.), chronic alcohol use, Wernicke encephalopathy, hepatic encephalopathy, diphenylhydantoin intoxication, drug abuse, immune-mediated inflammation, vitamin deficiency, superficial siderosis, and chronic CNS infection [
3] as determined through detailed history taking, blood tests, a nerve conduction study and examination of the cerebrospinal fluid, if necessary.
After the initial workup, 140 patients with cerebellar ataxia remained. The 140 patients were divided into 109 patients with sporadic cerebellar ataxia and 31 patients familial cerebellar ataxia as determined by a detailed history that covered over four generations (
Figure 1). Among patients with sporadic cerebellar ataxia, only one showed consanguinity (his parents are cousins). Based on the published criteria [
12], we excluded 73 patients who were diagnosed to have MSA-C. To ascertain the diagnosis, we performed an autonomic questionnaire and tests comprising a head-up tilt test, a urodynamics with sphincter electromyography [
13], and a sleep study when sleep apnea/nocturnal stridor was suspected. The remaining 67 patients comprised 36 patients with nonMSA-C sporadic cerebellar ataxia and 31 patients with familial cerebellar ataxia. Among the 36 nonMSA sporadic cerebellar ataxia patients, 28 patients (80%) requested gene analysis. Among the 31 familial cerebellar ataxia patients, 24 patients (77%) requested gene analysis. Therefore, in the present study, a total 52 patients (28 non-MSA-C sporadic cerebellar ataxia and 24 familial cerebellar ataxia patients) served as study subjects, with those patients diagnosed with familial cerebellar ataxia serving as controls. Statistical analysis was conducted using Student’s
t-test and Spearman’s rank correlation coefficient test.
RESULTS
- Patient demographics
Using the clinical-imaging features of 52 cerebellar ataxia patients, 39 patients had cortical cerebellar degeneration (CCA, or pure cerebellar form) [
14-
16]. Of these patients, 23 had sporadic cerebellar ataxia, and 16 had familial cerebellar ataxia 16. None of the patients had neurological signs other than cerebellar ataxia (except for mild frontal executive dysfunction and mild positional vertigo, both reported in CCA [
15]) by neurological examination and tests. None of the patients had atrophy/abnormal signals in brain areas other than the cerebellar hemisphere/vermis by MRI scans. Thirteen patients had non-CCA (sporadic 5, familial 8). Three of these 13 patients had extraocular movement abnormality, two had extrapyramidal sign, six had pyramidal sign, three had peripheral neuropathy, one had epilepsy, one had myoclonus, and one had decreased visual acuity. Brain MRI scans showed pontine atrophy in ten patients, and white matter lesions in one patient (
Table 1). We performed gene analysis comprising ten genes [SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA)] and CAG and TGGAA repeat length [
17], the details of which are described in our previous study [
18].
- Gene analysis results
In total, 34 (65%) of 52 cerebellar ataxia patients had gene abnormalities. SCA6 was the most common (17 patients, 32.7%), followed by SCA3 (6 patients, 11.5%), SCA31 (5 patients, 9.6%), SCA2 (2 patients, 3.8%), SCA1 (2 patients, 3.8%), SCA8 (1 patient, 1.9%), and DRPLA (1 patient, 1.9%). In the remaining patients, gene abnormalities were not identified. When divided by clinical-imaging subtypes, in non-CCA cases, gene abnormalities were found in 11/13 patients (85%). This is more than what was identified in CCA patients [23/39 patients (59%) (p < 0.05)]. Age at onset in CCA patients (mean, 55 years) was older than non-CCA patients (40 years), but the duration of the disease in CCA patients (mean, 12 years) was shorter than in non-CCA patients (15 years) (not statistically significant).
In non-MSA-C sporadic cerebellar ataxia, 16 (57%) of 28 patients had gene abnormalities. SCA6 was the most common (10 patients, 36%), followed by SCA1 (2 patients, 7.1%), SCA2 (1 patient, 3.6%), SCA3 (1 patient, 3.6%), SCA8 (1 patient, 3.6%), and DRPLA (1 patient, 3.6%). No abnormalities in SCA31 were observed. No gene abnormalities were identified in the remaining patients. When divided by clinical-imaging subtypes, in non-CCA patients, gene abnormalities were found in 5/5 (100%) patients. This is more than what was observed in CCA patients [11/23 patients (47.8%)]. SCA6 abnormalities were found in 10/23 patients (47.8%) with CCA (not statistically significant).
In familial cerebellar ataxia patients, 18 of 24 (75%) patients had gene abnormalities. SCA6 was most commonly mutated (7 patients, 29%), followed by SCA3 (5 patients, 20.8%), SCA31 (5 patients, 20.8%), SCA3 (1 patient, 3.6%), and SCA2 (1 patient, 4.2%). Gene abnormalities were not detected in remaining patients. All of the familial cerebellar ataxia cases might display autosomal dominant heredity. When divided by clinical-imaging subtypes, 5/7 (71%) nonCCA patients were shown to have gene abnormalities. This is almost the same as in CCA patients, which showed 13/17 (76%) of patients with abnormalities.
Among those with SCA6 (
n = 17), if we compare sporadic (
n = 10) versus familial cases (
n = 7), age at onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) (not statistically significant) (
Table 2).
DISCUSSION
The principal findings of this study can be summarized as follows: 1) Among non-MSA-C sporadic cerebellar ataxia, 57% of patients were found to have gene abnormalities. Among these, gene abnormalities in SCA6 were the most common (36%), followed by SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). No abnormalities in SCA7, 12, or 31 were detected. Thus, autosomal-dominant SCA mutations, particularly in SCA6, are not rare in sporadic cerebellar ataxia. 2) Among those with SCA6 (n = 17), when comparing sporadic versus familial cases, age at onset was older (69 years vs. 59 years, respectively), duration of disease was longer (17 years vs. 13 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively); however, these differences were not statistically significant.
To the best of our knowledge, this is the first study to show the frequency of autosomal-dominant SCA mutations in sporadic cerebellar ataxia by testing ten genes. The hereditary nature of the disorder has not been well recognized; however, we show a high frequency rate (57%) of autosomal dominant SCA gene abnormalities in sporadic cerebellar ataxia. This is in contrast to previous reports, showing a frequency of 2–18.8% [
1,
2,
5-
9]. While we do not know the exact reason for this discrepancy, one explanation is the different method of gene testing that was used. For example, we tested ten genes, which could increase the rate of detecting gene abnormalities. Additionally, familial relations may have been underreported in our subjects. Another explanation for the high frequency of SCA6 abnormalities is that this cohort had a higher age at onset and a variable penetrance of SCA6 abnormalities. This may also be attributable to the ethnicity or the geographical clustering of the families. SCA6 is the most common SCA subtype in Japan.
Because SCA6 seems to have the latest disease onset among all types of cerebellar ataxia [
9], mutations in the gene that causes SCA6 (
CACNA1A) might be found more frequently in sporadic cerebellar ataxia. The results of the present study confirmed this assumption, showing that SCA6 was the most common (36%) dominant SCA mutation in sporadic cerebellar ataxia. This finding is also noted by Abele et al. [
1].
Among those with SCA6, comparing sporadic versus familial cases, the age at onset was older (69 years vs. 59 years), and CAG repeat length was shorter (23 vs. 25, respectively) in the former. Thus, in SCA6, sporadic cases might have milder clinical-genetic feature than those of familial cases. However, this requires further clarification with a larger number of patients. This seems in accordance with the notion that developing SCA6 without a hereditary component could be due to a new mutation, or because of false paternity, incomplete penetrance and/or death of the transmitting parent before onset of clinical symptoms [
1-
3]. The present study results also prompted the assumption that there is an overlap between SCA6 and sporadic CCA [
14-
16,
19]. This is because SCA6 usually has the imaging findings and pathologic substrate confined to the cerebellar cortex.
Limitations of this study include that some of our patients underwent gene analysis at other institutions, and therefore, the number of triplet repeats is missing. This has the potential of interfering with the results of the clinical-genetic relationship. Additionally, we were unable to analyze additional SCA genes (for example, SCA11). Selection bias, such as the ambiguity of inclusion or exclusion and incomplete family history might also contribute to the discrepancy between the frequencies of gene abnormality in the present study and those in the previous studies. Although the number of our study subjects was small, our study results clearly indicate that autosomal-dominant SCA mutation, particularly SCA6, is not rare in SCA. This finding sheds light on proper patient care and the ability of early intervention of this disorder in the future.
In conclusion, autosomal-dominant SCA mutations, particularly SCA6, is not rare in sporadic cerebellar ataxia. The exact reason remains unclear, presumably reflecting higher age at onset and variable penetrance of SCA6.
Notes
-
Conflicts of Interest
The authors have no financial conflicts of interest.
Figure 1.Flow chart of patient recruitment. SCA: spinocerebellar ataxia, MSA-C: multiple system atrophy of cerebellar type.
Table 1.Gene analysis results and clinical-imaging features of spinocerebellar ataxia
Patient |
Age (years) |
Sex |
AAO (years) |
Disease duration (years) |
Gene analysis result
|
Inheritance |
Neurological examination
|
Neuroimaging
|
|
No. of repeat |
Cbll ataxia |
AbNL EOM |
EPS |
Pyramidal sign |
Neuropathy |
Personality change |
Cognitive decline |
Epilepsy |
Myoclonus |
Postural hypotension |
Others |
Cerebellar atrophy |
PA |
Others |
S1 |
39 |
M |
8 |
31 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S2 |
55 |
M |
45 |
10 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S3 |
59 |
M |
53 |
6 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S4 |
63 |
F |
62 |
1 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S5 |
66 |
M |
62 |
4 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S6 |
66 |
M |
48 |
18 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S7 |
68 |
F |
63 |
5 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S8 |
69 |
F |
64 |
5 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S9 |
75 |
M |
52 |
23 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S10 |
75 |
M |
62 |
13 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S11 |
76 |
F |
74 |
2 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S12 |
80 |
F |
79 |
1 |
ND |
|
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S13 |
65 |
M |
10 |
55 |
SCA1 |
NA |
Sporadic |
+ |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
S14 |
77 |
M |
75 |
2 |
SCA1 |
36 |
Sporadic |
+ |
+ |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
S15 |
56 |
M |
46 |
10 |
SCA2 |
38 |
Sporadic |
+ |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
S16 |
71 |
F |
66 |
5 |
SCA3 |
64 |
Sporadic |
+ |
- |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
S17 |
58 |
F |
44 |
14 |
SCA6 |
26 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S18 |
65 |
M |
47 |
18 |
SCA6 |
23 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S19 |
65 |
M |
41 |
25 |
SCA6 |
23 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S20 |
65 |
M |
43 |
22 |
SCA6 |
NA |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S21 |
69 |
M |
54 |
15 |
SCA6 |
26 |
Sporadic |
+ |
- |
- |
- |
- |
- |
+ |
- |
- |
- |
- |
+ |
- |
- |
S22 |
72 |
F |
50 |
22 |
SCA6 |
21 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S23 |
73 |
M |
56 |
17 |
SCA6 |
21 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S24 |
73 |
F |
65 |
8 |
SCA6 |
22 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S25 |
75 |
F |
69 |
6 |
SCA6 |
22 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S26 |
80 |
F |
66 |
16 |
SCA6 |
23 |
Sporadic |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
S27 |
58 |
M |
46 |
12 |
SCA8 homo |
128 |
Sporadic*
|
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Vertigo, loss of VS |
+ |
- |
- |
S28 |
16 |
F |
0 |
16 |
DRPLA |
67 |
Sporadic |
+ |
- |
- |
+ |
- |
- |
+ |
+ |
+ |
- |
Decreased visual acuity |
+ |
- |
WM lesion |
F1 |
38 |
F |
21 |
17 |
ND |
|
AD |
+ |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F2 |
59 |
M |
48 |
11 |
ND |
|
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F3 |
65 |
M |
40 |
25 |
ND |
|
AD |
+ |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F4 |
76 |
M |
69 |
7 |
ND |
|
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F5 |
79 |
M |
76 |
3 |
ND |
|
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F6 |
79 |
M |
72 |
7 |
ND |
|
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F7 |
60 |
F |
54 |
6 |
SCA2 |
37 |
AD |
+ |
- |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
F8 |
32 |
F |
18 |
14 |
SCA3 |
80 |
AD |
+ |
- |
+ |
+ |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
F9 |
44 |
M |
34 |
10 |
SCA3 |
71 |
AD |
+ |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
F10 |
54 |
M |
41 |
13 |
SCA3 |
NA |
AD |
+ |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
F11 |
70 |
M |
64 |
6 |
SCA3 |
61 |
AD |
+ |
- |
- |
- |
+ |
- |
- |
- |
- |
- |
- |
+ |
+ |
- |
F12 |
71 |
M |
51 |
20 |
SCA3 |
64 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Sleep apnea |
+ |
+ |
- |
F13 |
31 |
F |
29 |
2 |
SCA6 |
27 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F14 |
49 |
M |
36 |
13 |
SCA6 |
NA |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F15 |
61 |
M |
41 |
20 |
SCA6 |
24 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F16 |
63 |
F |
45 |
18 |
SCA6 |
26 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F17 |
64 |
M |
45 |
19 |
SCA6 |
NA |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F18 |
71 |
F |
60 |
11 |
SCA6 |
26 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F19 |
75 |
F |
70 |
5 |
SCA6 |
22 |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F20 |
70 |
M |
50 |
20 |
SCA31 |
Positive |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F21 |
70 |
M |
50 |
20 |
SCA31 |
Positive |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F22 |
74 |
M |
66 |
7 |
SCA31 |
Positive |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F23 |
74 |
M |
67 |
7 |
SCA31 |
Positive |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
F24 |
75 |
F |
74 |
1 |
SCA31 |
Positive |
AD |
+ |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+ |
- |
- |
Table 2.Comparison of sporadic and familial SCA6
Patient |
Age (years) |
Sex |
Age of onset (years) |
Disease duration (years) |
Gene analysis result
|
Familiality |
|
No. of repeat |
SP1 |
58 |
F |
44 |
14 |
SCA6 |
26 |
NO |
SP2 |
65 |
M |
47 |
18 |
SCA6 |
23 |
NO |
SP3 |
65 |
M |
41 |
25 |
SCA6 |
23 |
NO |
SP4 |
65 |
M |
43 |
22 |
SCA6 |
NA |
NO |
SP5 |
69 |
M |
54 |
15 |
SCA6 |
26 |
NO |
SP6 |
72 |
F |
50 |
22 |
SCA6 |
21 |
NO |
SP7 |
73 |
M |
56 |
17 |
SCA6 |
21 |
NO |
SP8 |
73 |
F |
65 |
8 |
SCA6 |
22 |
NO |
SP9 |
75 |
F |
69 |
6 |
SCA6 |
22 |
NO |
SP10 |
80 |
F |
66 |
16 |
SCA6 |
23 |
NO |
F1 |
31 |
F |
29 |
2 |
SCA6 |
27 |
YES |
F2 |
49 |
M |
36 |
13 |
SCA6 |
NA |
YES |
F3 |
61 |
M |
41 |
20 |
SCA6 |
24 |
YES |
F4 |
63 |
F |
45 |
18 |
SCA6 |
26 |
YES |
F5 |
64 |
M |
45 |
19 |
SCA6 |
NA |
YES |
F6 |
71 |
F |
60 |
11 |
SCA6 |
26 |
YES |
F7 |
75 |
F |
70 |
5 |
SCA6 |
22 |
YES |
REFERENCES
- 1. Abele M, Bürk K, Schöls L, Schwartz S, Besenthal I, Dichgans J, et al. The aetiology of sporadic adult-onset ataxia. Brain 2002;125:961–968.ArticlePubMedPDF
- 2. Abele M, Minnerop M, Urbach H, Specht K, Klockgether T. Sporadic adult onset ataxia of unknown etiology: a clinical, electrophysiological and imaging study. J Neurol 2007;254:1384–1389.ArticlePubMedPDF
- 3. Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 2010;9:94–104.ArticlePubMed
- 4. Tsuji S, Onodera O, Goto J, Nishizawa M; Study Group on Ataxic Diseases. Sporadic ataxias in Japan--a population-based epidemiological study. Cerebellum 2008;7:189–197.ArticlePubMed
- 5. Ranum LP, Lundgren JK, Schut LJ, Ahrens MJ, Perlman S, Aita J, et al. Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia. Am J Hum Genet 1995;57:603–608.PubMedPMC
- 6. Moseley ML, Benzow KA, Schut LJ, Bird TD, Gomez CM, Barkhaus PE, et al. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998;51:1666–1671.ArticlePubMed
- 7. Pujana MA, Corral J, Gratacís M, Combarros O, Berciano J, Genòs D, et al. Spinocerebellar ataxias in Spanish patients: genetic analysis of familial and sporadic cases. The Ataxia Study Group. Hum Genet 1999;104:516–522.ArticlePubMed
- 8. Wang J, Shen L, Lei L, Xu Q, Zhou J, Liu Y, et al. Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011;36:482–489.PubMed
- 9. Lindquist SG, Nørremølle A, Hjermind LE, Hasholt L, Nielsen JE. Meiotic CAG repeat instability in spinocerebellar ataxia type 6: maternally transmitted elongation in a presumed sporadic case. J Neurol Sci 2006;241:95–98.ArticlePubMed
- 10. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.ArticlePubMed
- 11. Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology 2000;55:1621–1626.ArticlePubMed
- 12. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670–676.ArticlePubMedPMC
- 13. Sakakibara R, Uchiyama T, Yamanishi T, Kishi M. Sphincter EMG as a diagnostic tool in autonomic disorders. Clin Auton Res 2009;19:20–31.ArticlePubMedPDF
- 14. Tsuchiya K, Ozawa E, Saito F, Irie H, Mizutani T. Neuropathology of late cortical cerebellar atrophy in Japan: distribution of cerebellar change on an autopsy case and review of Japanese cases. Eur Neurol 1994;34:253–262.ArticlePubMed
- 15. Mascalchi M, Vella A. Magnetic resonance and nuclear medicine imaging in ataxias. Handb Clin Neurol 2012;103:85–110.ArticlePubMed
- 16. Klockgether T. Sporadic adult-onset ataxia of unknown etiology. Handb Clin Neurol 2012;103:253–262.ArticlePubMed
- 17. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 1997;15:62–69.ArticlePubMedPDF
- 18. Ishige T, Sawai S, Itoga S, Sato K, Utsuno E, Beppu M, et al. Pentanucleotide repeat-primed PCR for genetic diagnosis of spinocerebellar ataxia type 31. J Hum Genet 2012;57:807–808.ArticlePubMedPDF
- 19. Tsuchiya K, Oda T, Yoshida M, Sasaki H, Haga C, Okino H, et al. Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on disease duration: report of two autopsy cases and statistical analysis of autopsy cases reported to date. Neuropathology 2005;25:125–135.ArticlePubMed
Citations
Citations to this article as recorded by
- Genetic profiles of multiple system atrophy revealed by exome sequencing, long‐read sequencing and spinocerebellar ataxia repeat expansion analysis
Xu‐Ying Li, Hong Lai, Xian Li, Fanxi Xu, Yang Song, Zhanjun Wang, Qibin Li, Ruichai Lin, Zhiheng Xu, Chaodong Wang
European Journal of Neurology.2024;[Epub] CrossRef - MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias
Mario Mascalchi
Tomography.2022; 8(1): 423. CrossRef - An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary
Norlinah Mohamed Ibrahim
Parkinsonism & Related Disorders.2022; 105: 157. CrossRef - A novel clinicopathologic entity causing rapidly progressive cerebellar ataxia?
Shunsuke Koga, Shan Ali, Matthew C. Baker, Klaas J. Wierenga, Michelle Dompenciel, Dennis W. Dickson, Zbigniew K. Wszolek
Parkinsonism & Related Disorders.2022; 105: 149. CrossRef - The First Case of Spinocerebellar Ataxia Type 8 in Monozygotic Twins
Jun Sawada, Takayuki Katayama, Takashi Tokashiki, Shiori Kikuchi, Kohei Kano, Kae Takahashi, Tsukasa Saito, Yoshiki Adachi, Yuji Okamoto, Akiko Yoshimura, Hiroshi Takashima, Naoyuki Hasebe
Internal Medicine.2020; 59(2): 277. CrossRef - The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review
Shirley Yin-Yu Pang, Kay-Cheong Teo, Jacob Shujui Hsu, Richard Shek-Kwan Chang, Miaoxin Li, Pak-Chung Sham, Shu-Leong Ho
Translational Neurodegeneration.2017;[Epub] CrossRef