Background
Methods
Subjects and controls
Detection of rare copy number variants
Case | Sample ID | Sex | Onset (year) | CNV type | Locationa
| Size (kb) | Genes | CNV source | Exome seq |
---|---|---|---|---|---|---|---|---|---|
De novo
| |||||||||
A | 8961143 | F | 6 | dup | Xp22.31 | 305 |
VCX3B, KAL1
|
de novo
| ✓ |
B | 896993 | M | 8 | del | 4p16.3 | 165 |
ADRA2C
|
de novo
| |
dup | 3p26.3 | 1735 |
CNTN6, CNTN4
| pat | |||||
C | 1254 (188613) | M | 3 | del | 3p12.2 | 182 | – |
de novo
| ✓ |
del | 3q26.31 | 142 |
NLGN1
| mat | |||||
del | 7q36.2 | 115 |
DPP6
| mat | |||||
dup | 7q36.3 | 67 |
PTPRN2
b
| pat | |||||
D | 896713 | F | 10 | dup (mosaic) | 10q11.22- q11.21 | 239 |
ZFAND4, FAM21C, MARCH8
|
de novo
| nsf c
|
dup | 10q24.1 | 81 |
SLIT1
b
| mat | |||||
Overlap with curated DECIPHER syndromesd
| |||||||||
E | HAM493 | F | 8 | dup | 15q11.2-q13.1 | 4918 | 13 genes | n/a | |
F | 0625-4262-1 | M | 8 | dup | 1q21.1-21.2 | 1799 | 15 genes | mat | ✓ |
G | 1648 | F | 12 | del | 17p12 | 1404 | 8 genes | mat | ✓ |
dup | 5p11-p12 e
| 1065 |
HCN1
b
| pat | |||||
H | 896573 | M | 9 | dup | 16p13.11 | 783 | 8 genes | mat | nsf |
Genes implicated in other neurodevelopmental disorders | |||||||||
I | 1298 | M | 5 | dup | Xp22.31 | 338 |
NLGN4X
| mat | ✓ |
J | 896673_a | M | 12 | del | 9q33.1 | 173 |
ASTN2, TRIM32
| n/a | |
K | 7542 | M | 12 | del | 9q33.1 | 163 |
ASTN2, TRIM32
b
| n/a | |
L | 0625-3695-3 | M | 12 | dup | 12q24.33 | 682 |
TMEM132D
| mat | ✓ |
M | 1688 | F | 3 | del | 18q22.1 | 2126 |
CDH19, CDH7
| mat | |
FMRP target genes | |||||||||
N | HAM193 | M | 12 | dup | 9p24.1 | 1489 |
PTPRD, C9orf123
| n/a | |
O | 896553 | F | 6 | del | 8p23.3 | 16 |
DLGAP2
| pat | ✓ |
P | 1213 | M | 4 | dup | 18p11.31 | 62 |
DLGAP1
| pat | ✓ |
Overlap BTBD9
| |||||||||
Q | 0625-3790-3 | F | 8 | del | 6p21.2 | 107 |
BTBD9
| pat | |
R | 0625-7518-3 | F | 7 | dup | 6p21.2 | 469 |
GLO1, DNAH8, BTBD9
| pat |
Burden of CNVs in cases and controls
Gene set enrichment analysis
Exome sequencing
Case | Sample ID | Position | Gene | Isoform | Change | Effect | Source | RVIS (%)a
| pLIb
|
---|---|---|---|---|---|---|---|---|---|
A | 8961143 | chr4:69,403,498-69,403,498 |
UGT2B17
| NM_001077 | p.A480T | Missense |
de novo
| 96.5 | 0.01 |
G | 1648 | chr18:3,102,478 |
MYOM1
| NM_003803 | p.G1190A | Missense |
de novo
| 81.7 | 0.00 |
chrX:114,347,884-114,347,887 |
LRCH2
| NM_020871 | p.C730fs | Frameshift del |
de novo
| 53.2 | 0.92 | ||
J | 896553 | chr14:24,677,345 |
TSSK4
| NM_001184739 | p.T337M | Missense |
de novo
| 77.7 | 0.00 |
chr14:74,947,404 |
NPC2
| NM_006432 | c.548 + 1C > T | Splice site | mat | 71.1 | 0.01 | ||
K | 1213 | chr9:2,824,808 |
KIAA0020
| NM_014878 | p.I348N | Missense |
de novo
| 78.9 | 0.00 |
R | 0625-3695-3 | chr9:107,266,546 |
OR13F1
| NM_001004485 | p.M1I | Missense |
de novo
| 95.9 | 0.00 |
USP54
| NM_152586 | p.R1395X | Nonsense | pat | 91.4 | 0.00 | |||
C | 1254 | chrX:148,048,382-148,048,393 |
AFF2
| NM_002025 | p.992_996del | Deletion | mat | 7.2 | 1.00 |
chr11:637,537-637,549 |
DRD4
| NM_000797 | p.A78fs | Frameshift del | mat | N/A | 0.00 | ||
chr3:129,155,547 |
MBD4
| NM_003925 | p.E314fs | Frameshift ins | mat | 83.4 | 0.00 | ||
F | 0625-4262-1 | chr5:145,895,394 |
GPR151
| NM_194251 | p.R95X | Nonsense | mat | 78.7 | 0.00 |
O | 1298 | chr19:11,325,007 |
DOCK6
| NM_020812 | p.Q1428X | Nonsense | mat | 9.4 | 0.00 |
Results
Rare copy number variations
Exome sequencing
Gene set enrichment
Gene set | Size of gene set | With known locia
| Without known loci | ||
---|---|---|---|---|---|
Nominal p value | False discovery rate (FDR) | Nominal p value | FDR | ||
FMR1 targetsb
| 840 | 0.00185 | 0.09 | 0.00312 | 0.16 |
Nervous system developmentc
| 1,874 | 0.0186 | 0.26 | 0.0633 | 0.46 |
Union inclusived
| 2,874 | 0.0205 | 0.26 | 0.0385 | 0.35 |