General information of case group
111 of the 114 TD patients were followed up, with a male to female ratio of 4.3:1, of which 89 were newly diagnosed. Among the 111 children, 32were consistent with TTD, 45 with CTD, and 34with TS, among which 16 were 3–5 years old, 59 were 6–8 years old, 27 were 9–11 years old, 8 were 12–14 years old, and 1 was 15 years old. The composition of the three groups of TD children in different age groups was shown in Fig. 1. Children in the TTD group ranged in age from 3 to 12 years old, with an average age of 7.58 ± 2.402 years old and a male to female ratio of 5.4:1. In the CTD group, the children ranged in age from 5 to 14 years old, with an average age of 8.72 ± 2.312 years old and a male to female ratio of 2.75:1. The age range of children in TS group was 4–15 years old, with an average age of 8.85 ± 2.720 years old, and the ratio of male to female was 7.5:1.
Clinical manifestations of three groups of children
The clinical manifestations of 111 TD children in this group are diverse, with more than 30 kinds of muscle twitch. There were 47 cases of forced blinking (TTD 16 cases, CTD 19 cases and TS 12 cases), There were 47 cases of forced blinking (TTD 16 cases, CTD 19 cases and TS 12 cases), 33 cases of shrug nose (TTD 4 cases, CTD 12 cases and TS 17 cases), 24 cases of mouth twitch/crooked mouth (TTD 5 cases, CTD 15 cases and TS 4 cases), and 21 cases of shrug (TTD 6 cases, CTD 5 cases and TS 10 cases). 1 case of CTD and 3 cases of TS underwent cranial MR examination, and the results were normal. There were 12 TD children with video EEG, among which 1 had abnormal results (a small amount of medium-high amplitude and slow wave emission in the right central area and the back head during waking and sleeping), and the rest were normal. The clinical manifestations of 111 children with TD in different groups are shown in Table 1.
Comparison of genotype frequency and gene frequency of COL27A1 rs4979356, rs4979357 and rs7868992 between TD children and control group
The genotype frequency and gene frequency of COL27A1 rs4979356, rs4979357 and rs7868992 in the case group and the control group showed no statistically significant difference (P > 0.05). See Table 1 for details.
Comparison of genotype frequency and gene frequency of COL27A1 rs4979356, rs4979357 and rs7868992 in three sub-groups of children with TD
Genotype frequency and gene frequency of COL27A1 rs4979356 were compared among three groups of children with TD and healthy control group
In TTD group, CC genotype accounted for 8 cases, CG genotype accounted for 17 cases, GG genotype accounted for 7 cases, allele frequency C33 (51.6%), G31 (48.4%); CTD group: CC genotype accounted for 18 cases, CG genotype accounted for 19 cases, GG genotype accounted for 8 cases, allele frequency C55 (61.1%), G35 (38.9%); TS group: CC genotype accounted for 3 cases, CG genotype accounted for 28 cases, GG genotype accounted for 3 cases, allele frequency C34 (5 In healthy control group, CC genotype accounted for 31 cases, CG genotype accounted for 46 cases, GG genotype accounted for 23 cases, allele frequency C108 (54.0%), G92 (46.0%). The distribution of genotype CG in TS group was higher than that in TTD + CTD group (χ2 = 12.452, P = 0.002) and control group (χ2 = 13.618, P = 0.001), and the difference was statistically significant (P < 0.05). There was no significant difference in allele frequency between groups (P > 0.05). See Tables 3 and 4 for details.
Table 3
Comparison of genotype frequency and gene frequency of COL27A1 rs4979356, rs4979357 and rs7868992 between TTD + CTD group and TS group
SNPs
|
genotype/allele
|
TTD + CTD group(n)
|
TS group(n)
|
χ2value
|
P value
|
rs4979356
|
genotype
|
CC
|
26
|
3
|
12.452
|
0.002
|
|
|
CG
|
36
|
28
|
|
|
|
|
GG
|
15
|
3
|
|
|
|
allele
|
C
|
88
|
34
|
0.972
|
0.324
|
|
|
G
|
66
|
34
|
|
|
rs4979357
|
genotype
|
TT
|
24
|
3
|
10.814
|
0.004
|
|
|
TC
|
38
|
28
|
|
|
|
|
CC
|
15
|
3
|
|
|
|
allele
|
T
|
88
|
34
|
0.649
|
0.421
|
|
|
C
|
68
|
34
|
|
|
rs7868992
|
genotype
|
GG
|
38
|
8
|
8.034
|
0.018
|
|
|
GA
|
32
|
24
|
|
|
|
|
AA
|
7
|
2
|
|
|
|
allele
|
G
|
108
|
40
|
2.714
|
0.100
|
|
|
A
|
46
|
28
|
|
|
Table 4
Comparison of genotype frequency and gene frequency of COL27A1 rs4979356, rs4979357 and rs7868992 between TS group and control group
SNPs
|
genotype/allele
|
TS group(n)
|
control group(n)
|
χ2value
|
P value
|
rs4979356
|
genotype
|
CC
|
3
|
31
|
13.618
|
0.001
|
|
|
CG
|
28
|
46
|
|
|
|
|
GG
|
3
|
23
|
|
|
|
allele
|
C
|
34
|
108
|
0.326
|
0.568
|
|
|
G
|
34
|
92
|
|
|
rs4979357
|
genotype
|
TT
|
3
|
31
|
13.618
|
0.001
|
|
|
TC
|
28
|
46
|
|
|
|
|
CC
|
3
|
23
|
|
|
|
allele
|
T
|
34
|
108
|
0.326
|
0.568
|
|
|
C
|
34
|
92
|
|
|
rs7868992
|
genotype
|
GG
|
8
|
42
|
6.695
|
0.035
|
|
|
GA
|
24
|
45
|
|
|
|
|
AA
|
2
|
13
|
0.702
|
0.402
|
|
allele
|
G
|
40
|
129
|
|
|
|
|
A
|
28
|
71
|
|
|
Genotype frequency and gene frequency of COL27A1 rs4979357 were compared among three groups of children with TD and healthy control group
In TTD group: TT genotype accounted for 8 cases, TC genotype accounted for 17 cases, CC genotype accounted for 7 cases, allele frequency T33 (51.6%), C31 (48.4%). In the CTD group, TT genotype accounted for 16 cases, TC genotype for 21 cases, CC genotype for 8 cases, allele frequency T53 (58.9%), C37 (41.1%). In TS group, TT genotype accounted for 3 cases, TC genotype for 28 cases, CC genotype for 3 cases, allele frequency T34 (50.0%), C34 (50.0%). In the healthy control group, TT genotype accounted for 31 cases, TC genotype for 46 cases, CC genotype for 23 cases, allele frequency T108 (54.0%), C92 (46.0%). Genotype TC distribution in TS group was higher than that in TTD + CTD group (χ2 = 10.814, P = 0.004) and control group (χ2 = 13.618, P = 0.001), with statistically significant difference (P < 0.05). There was no significant difference in allele frequency between groups (P > 0.05). See Table 3 and Table 4 for details.
Genotype frequency and gene frequency of COL27A1rs7868992were compared among three groups of children with TD and healthy control group
In TTD group: GG genotype accounted for 12 cases, GA genotype accounted for 16 cases, AA genotype accounted for 4 cases, allele frequency G40 (62.5%), A24 (37.5%); CTD group: GG genotype accounted for 26 cases, GA genotype accounted for 16 cases, AA genotype accounted for 3 cases, allele frequency g68 (75.6%), A22 (24.4%); ts group: GG genotype accounted for 8 cases, GA genotype accounted for 24 cases, AA genotype accounted for 2 cases, allele frequency G40( In healthy control group, GG genotype accounted for 42 cases, GA genotype accounted for 45 cases, AA genotype accounted for 13 cases, allele frequency G129 (64.5%), a71 (35.5%); genotype GA in TS group was higher than that in TTD group + CTD group (χ2 = 8.034, P = 0.018) and control group χ2 = 6.695, P = 0.035), the difference was statistically significant (P < 0.05). The distribution of G allele frequency in CTD group was higher than that in TS group, the difference was statistically significant (χ2 = 5.013, P = 0.025), and there was no significant difference in other allele frequencies between the two groups (P > 0.05). See Tables 3 and 4 for details.