Background
Methods
Population and patient samples
Ethical approval
MLPA technique
Statistical analysis
Results
Gene copy number and structure in SMA patients
MLPA probe copy number | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Total | SMN1/SMN2 |
SMN1
|
SMN2
|
NAIP
| |||||||
Group | N = 42 | Exon1 | Exon4 | Exon6 | Exon8 | Exon7 | Exon8 | Exon7 | Exon8 | Exon13 | Exon5 |
1 | 3(7.1%) | 2 | 2 | 2 | 2 | 0 | 0 | 2 | 2 | 1 | 1 |
2 | 3(7.1%) | 2 | 2 | 2 | 2 | 0 | 0 | 2 | 2 | 1 | 0 |
3 | 1(2.4%) | 2 | 2 | 2 | 2 | 0 | 1 | 2 | 1 | 1 | 0 |
4 | 1(2.4%) | 2 | 2 | 2 | 2 | 0 | 0 | 2 | 2 | 2 | 1 |
5 | 1(2.4%) | 3 | 3 | 3-4 | 3 | 0 | 0 | 3 | 3 | 2 | 1 |
6 | 1(2.4%) | 3 | 3 | 3-4 | 3 | 0 | 0 | 3 | 3 | 2 | 2 |
7 | 4(9.5%) | 3 | 3 | 3 | 3-4 | 0 | 0 | 3 | 3 | 2 | 2 |
8 | 2(4.8%) | 4 | 4 | 4 | 4 | 0 | 0 | 4 | 4 | 2 | 2 |
9 | 1(2.4%) | 3 | 3-4 | 3 | 3 | 0 | 1 | 2 | 2 | 2 | 1 |
10 | 2(4.8%) | 3 | 3-4 | 3-4 | 3 | 0 | 0 | 2 | 3 | 2 | 2 |
11 | 9(21.3%) | 3 | 3-4 | 3 | 3-4 | 0 | 0 | 3 | 3 | 2 | 1 |
12 | 6(14.2%) | 3 | 3 | 3 | 3 | 0 | 0 | 3 | 3 | 1 | 1 |
13 | 1(2.4%) | 3 | 3 | 3 | 3 | 0 | 1 | 3 | 2 | 1 | 1 |
14 | 1(2.4%) | 2 | 2 | 2 | 2 | 0 | 1 | 2 | 1 | 1 | 1 |
15 | 1(2.4%) | 2-3 | 2-3 | 3 | 4 | 0 | 0 | 3 | 4 | 2 | 2 |
16 | 2(4.8%) | 2-3 | 3 | 3 | 3-4 | 0 | 0 | 3 | 4 | 2 | 1 |
17 | 2(4.8%) | 1-2 | 2 | 2 | 2 | 0 | 0 | 2 | 2-3 | 2 | 2 |
18 | 1(2.4%) | 2-3 | 2-3 | 3 | 3 | 0 | 1 | 3 | 2 | 2 | 1 |
Total | Gene copy number | ||||||
---|---|---|---|---|---|---|---|
Pattern | Group | N = 42 | NormalSMN1gene | NormalSMN2gene | NormalNAIPgene | HybridSMNgene | Gene lacking partial sequences |
A | 1 | 3(7.1%) | 0 | 2 | 1 | 0 | 0 |
B | 2 | 3(7.1%) | 0 | 2 | 0 | 0 | 1
a
|
C | 3 | 1(2.4%) | 0 | 1 | 0 | 1
e
| 1
a
|
D | 4 | 1(2.4%) | 0 | 2 | 1 | 0 | 1
a
|
E | 5 | 1(2.4%) | 0 | 3 | 1 | 0 | 1
a
|
F | 6/7 | 5(11.9%) | 0 | 3 | 2 | 0 | 0 |
G | 8 | 2(4.8%) | 0 | 4 | 2 | 0 | 0 |
H | 9 | 1(2.4%) | 0 | 2 | 1 | 0 | 1
a
and 1
b
|
I | 10 | 2(4.8%) | 0 | 2 | 2 | 0 | 1
c
|
J | 11 | 9(21.3%) | 0 | 3 | 1 | 0 | 1
a
|
K | 12 | 6(14.2%) | 0 | 3 | 1 | 0 | 0 |
L | 13 | 1(2.4%) | 0 | 2 | 1 | 1
e
| 0 |
M | 14 | 1(2.4%) | 0 | 1 | 1 | 1
e
| 0 |
N | 15 | 1(2.4%) | 0 | 3 | 2 | 0 | 1
d
|
O | 16 | 2(4.8%) | 0 | 3 | 1 | 0 | 1
a
and 1
d
|
P | 17 | 2(4.8%) | 0 | 2 | 2 | 0 | 0 |
Q | 18 | 1(2.4%) | 0 | 2 | 1 | 1
f
| 1
a
|
Gene copy number and structure analysis of unrelated healthy individuals
MLPA probe copy number | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Total | SMN1/SMN2 |
SMN1
|
SMN2
|
NAIP
| |||||||
Group | N = 212 | Exon1 | Exon4 | Exon6 | Exon8 | Exon7 | Exon8 | Exon7 | Exon8 | Exon13 | Exon5 |
1 | 117(55.2%) | 4-5 | 4-5 | 4 | 4-5 | 2 | 2 | 2 | 2 | 2 | 2 |
2 | 1(0.5%) | 4 | 4 | 4 | 4 | 2 | 3 | 2 | 1 | 2 | 2 |
3 | 1(0.5%) | 4 | 4-5 | 4 | 4 | 2 | 1 | 2 | 3 | 2 | 2 |
4 | 54(25.4%) | 3-4 | 3-4 | 3 | 3-4 | 2 | 2 | 1 | 1 | 2 | 2 |
5 | 1(0.5%) | 3 | 3 | 3 | 3 | 2 | 3 | 1-2 | 0 | 2 | 2 |
6 | 7(3.3%) | 3-4 | 3 | 3-4 | 3-4 | 2 | 2 | 1 | 1 | 2 | 3 |
7 | 1(0.5%) | 3-4 | 3-4 | 3-4 | 3 | 2 | 2 | 1 | 1 | 2 | 4 |
8 | 4(1.9%) | 2 | 2 | 2 | 2 | 2 | 2 | 0 | 0 | 1 | 2 |
9 | 5(2.3%) | 2 | 2-3 | 2-3 | 2-3 | 2 | 2 | 0 | 0 | 1 | 3 |
10 | 1(0.5%) | 3 | 3 | 3-4 | 3-4 | 2 | 2 | 1 | 1 | 1 | 1 |
11 | 5(2.3%) | 4 | 4-5 | 4 | 4 | 2 | 2 | 2 | 2 | 2 | 3 |
12 | 1(0.5%) | 4 | 4-5 | 4 | 4-5 | 2 | 1 | 2 | 3 | 2 | 3 |
13 | 2(0.9%) | 4 | 4-5 | 4 | 4-5 | 2 | 3 | 2 | 1 | 2 | 3 |
14 | 2(0.9%) | 4 | 4 | 4 | 4 | 3 | 3 | 1 | 1 | 2 | 2 |
15 | 3(1.4%) | 4 | 4-5 | 4 | 4-5 | 2 | 2 | 2 | 2 | 2 | 1 |
16 | 2(0.9%) | 4-5 | 5 | 5 | 4-5 | 2 | 2 | 3 | 3 | 2 | 2 |
17 | 1(0.5%) | 4 | 4-5 | 4 | 5 | 1 | 2 | 1 | 2 | 2 | 2 |
18 | 1(0.5%) | 4-5 | 5 | 5 | 4-5 | 3 | 3 | 2 | 2 | 2 | 3 |
19 | 1(0.5%) | 4-5 | 5 | 4-5 | 5 | 3 | 3 | 2 | 2 | 2 | 1 |
20 | 1(0.5%) | 3 | 3-4 | 3-4 | 3-4 | 1 | 1 | 2 | 2 | 2 | 1 |
21 | 1(0.5%) | 4 | 4 | 4 | 4 | 3 | 3 | 1 | 1 | 2 | 3 |
Total | Gene copy number | ||||||
---|---|---|---|---|---|---|---|
Pattern | Group | N = 212 | NormalSMN1gene | NormalSMN2gene | NormalNAIPgene | HybridSMNgene | Gene lacking partial sequences |
A | 1 | 117(55.2%) | 2 | 2 | 2 | 0 | 0 |
B | 2 | 1(0.5%) | 2 | 1 | 2 | 1
e
| 0 |
C | 3 | 1(0.5%) | 1 | 2 | 2 | 1
h
| 0 |
D | 4 | 54(25.5%) | 2 | 1 | 2 | 0 | 0 |
E | 5 | 1(0.5%) | 2 | 0 | 2 | 1
e
| 0 |
F | 6/7 | 8(3.8%) | 2 | 1 | 2 | 0 | 1
g
|
G | 8/9 | 9(4.2%) | 2 | 0 | 1 | 0 | 1
g
|
H | 10 | 1(0.5%) | 2 | 1 | 1 | 0 | 0 |
I | 11 | 5(2.3%) | 2 | 2 | 2 | 0 | 1
g
|
J | 12 | 1(0.5%) | 1 | 2 | 2 | 1
h
| 1
g
|
K | 13 | 2(0.9%) | 2 | 1 | 2 | 1
e
| 1
g
|
L | 14 | 2(0.9%) | 3 | 1 | 2 | 0 | 0 |
M | 15 | 3(1.4%) | 2 | 2 | 1 | 0 | 1
a
|
N | 16 | 2(0.9%) | 2 | 3 | 2 | 0 | 0 |
O | 17 | 1(0.5%) | 1 | 1 | 2 | 0 | 1
b
and 1
c
|
P | 18 | 1(0.5%) | 3 | 2 | 2 | 0 | 1
g
|
Q | 19 | 1(0.5%) | 3 | 2 | 1 | 0 | 1
a
|
R | 20 | 1(0.5%) | 1 | 2 | 1 | 0 | 1
a
|
S | 21 | 1(0.5%) | 3 | 1 | 2 | 0 | 1
g
|
Differences in distribution of participants by SMN2 and NAIP gene copy numbers
Number of normalSMN2 | SMA patients (N = 42) | Healthy individuals (N = 212) |
P
|
---|---|---|---|
0 | 0 (0%) | 10 (4.7%) | |
1 | 2 (4.8%) | 70 (33.1%) | |
2 | 14 (33.3%) | 130 (61.3%) | <0.001 |
3 | 24 (57.1%) | 2 (0.9%) | |
4 | 2 (4.8%) | 0 (0%) |
Number of normalNAIP | SMA patients (N = 42) | Healthy individuals (N = 212) |
P
|
---|---|---|---|
0 | 4 (9.5%) | 0 (0%) | |
1 | 26 (61.9%) | 15 (7.1%) | <0.001 |
2 | 12 (28.6%) | 197 (92.9%) |