Table 1.
Summary of clinically significant copy number variants (CNVs) identified in 27 out of 511 patients with NDDs
| Patient ID | Clinical information | ISCN nomenclature | Chromosome locations/Size of alterations | Candidate genes | Genetic diagnosis | Studies that previously report CNVs |
|---|---|---|---|---|---|---|
| 89 | 2 year old male with global developmental delay, hypotonia | arr[GRCh37] 2q23.3q24.1(152826896_157180476) × 1 |
2q23.3–2q24.1: 4.4 Mb deletion |
CACNB4, KCNJ3, PRPF40A, FMNL2 | 2q23.3–2q24.1 deletion | This study |
| 319 | 4 year old male with global developmental delay, speech delay, dysmorphic craniofacial features |
arrh[GRCh37] 5p15.33(25328_1721527) × 3, 18p11.32(13034_2243990) × 1 |
5p15.33: 1.7 Mb duplication; 18p11.32: 2.2 Mb deletion |
SLC6A19, TERT | Unbalanced translocation der(18)t(5;18)(p15.33;p11.32) | This study |
| 267 | 10 year old male with mild intellectual disability, hypotonia, abnormal MRI (small left medial cerebellar hemisphere, hypoplastic right olfactory bulb and incomplete myelination of temporal lobes), gross motor impairment, fine motor impairment | arr[GRCh37] 6q16.1q16.3(95913318_104980478) × 1 |
6q16.1–6q16.3: 9.1 Mb deletion |
SIM1, GRIK2, FBXL4, NDUFAF4 | 6q16.1–6q16.3 deletion | This study; CNVs overlapping with this deletion reported previously (Bonaglia et al., 2008; Kasher et al., 2016; Strunk et al., 2016) |
| 29 | 3 year old male with congenital atresia of esophagus, tracheomalacia, tracheoesophageal fistula, feeding problem, gastroesophageal reflux disease, abnormal posture, oropharyngeal phase dysphagia, mixed receptive-expressive language disorder | arr[GRCh37] 7q11.22(69564501_69795311) × 1 |
7q11.22: 230.8 Kb deletion |
AUTS2 | AUTS2 syndrome | (Amarillo et al., 2014; Beunders et al., 2016; Beunders et al., 2013; Liu et al., 2015) |
| 303 | 3 year old male with global developmental delay, aortic arch hypoplasia, moderate right, mild left branch pulmonary artery stenosis | arr[GRCh37] 7q11.23(72722981_74141840) × 1 |
7q11.23: 1.4 Mb deletion |
ELN | Williams-Beuren syndrome | (Pober, 2010; Samanta, 2017) |
| 367 | 6 year old male with transient neonatal hypoglycemia, muscle weakness, oral phase dysphagia, speech disturbance, motor skills developmental delay, feeding difficulties, astigmatism, lack of coordination, hyperopia, sensory processing difficulty | arr[GRCh37] 9p24.3p23(46587_13422337) × 1 |
9p24.3–9p23: 13.4 Mb deletion |
Many (genes) | 9p deletion syndrome | (Bayat et al., 2018; Sivasankaran et al., 2016; Spazzapan et al., 2016; Tassano et al., 2016) |
| 270 | 18 year old male with autism | arr[GRCh37] 11p11.2(44222462_44236652) × 1 |
11p11.2: 14 Kb deletion |
EXT2 | Hereditary multiple osteochondromas | (D’Arienzo et al., 2019; Jennes et al., 2008) |
| 283 | 21 month old female with developmental delay, decreased motor activity, gross motor development delay | arr[GRCh37] 15q13.2q13.3(30657952_32833659) × 1 |
15q13.2–15q13.3: 2.2 Mb deletion |
CHRNA7 | 15q13.3 microdeletion syndrome | (Ben-Shachar et al., 2009; Hoppman-Chaney et al., 2013; Lowther et al., 2015; Ziats et al., 2016) |
| 361 | 5 year old male with closed fracture of shaft of clavicle, mixed receptive-expressive language disorder, speech disturbances, autism spectrum disorder, global developmental delay | arr[GRCh37] 15q13.2q13.3(30737344_32514341) × 1 |
15q13.2–15q13.3: 1.8 Mb deletion |
CHRNA7 | 15q13.3 microdeletion syndrome | |
| 506 | 4 year old male with global developmental delay, family history of intellectual disabilities | arr[GRCh37] 15q13.2q13.3(30936285_32514341) × 1 |
15q13.2–15q13.3: 1.6 Mb deletion |
CHRNA7 | 15q13.3 microdeletion syndrome | |
| 453 | 6 year old male with global developmental delay, hypopigmentation |
arr[GRCh37] 15q11.2(22750305_23272733) × 1, 15q13.3(32018731_32514341) × 1, 10q26.12q26.2(122879869_128014502) × 2 hmz |
15q11.2: 522 Kb deletion; 15q13.3: 496 Kb deletion; 10q26.12q26.2: 5.1 Mb LOH |
CHRNA7 | 15q13.3 microdeletion syndrome | |
| 313 | 8 year old female with mixed receptive-expressive language disorder, epilepsy, language regression | arr[GRCh37] 16p11.2(29595483_30198151) × 3 |
16p11.2: 603 Kb duplication |
TBX6, KIF22, PRRT2 | 16p11.2 microduplication | (D’Angelo et al., 2016; Kumar et al., 2009; Shinawi et al., 2010; Weiss et al., 2008) |
| 488 | 14 year old male with congenital hypogonadotropic hypogonadism, micropenis, autism spectrum disorder |
arr[GRCh37] 16p11.2(29595483_29733442) × 4, 16p11.2(29763089_30198151) × 4 |
16p11.2: 138 Kb triplication 16p11.2: 435 Kb triplication |
TBX6, KIF22, PRRT2 | 16p11.2 triplication | This study |
| 31 | 4 year old female with speech delay, low carnitine, language disorder | arr[GRCh37] 16p13.11(14968859_16291983) × 1 |
16p13.11: 1.3 Mb deletion |
NDE1, MYH11, PXE, ABCC6 | 16p13.1 deletion | This study; CNVs overlap with the 1.5 Mb neurocognitive susceptibility locus on 16p13.11 (Liu et al., 2012; Tan et al., 2017) |
| 129 | 12 year old male with global developmental delay, obesity with serious comorbidity and body mass index (BMI) greater than 99th percentile for age in pediatric patient, Charcot-Marie-Tooth disease (CMT), overgrowth syndrome | arr[GRCh37] 17p12(14095309_15471179) × 3 |
17p12: 1.4 Mb duplication |
PMP22 | Charcot-Marie-Tooth disease type 1A (CMT1A) | (Laura et al., 2019; Morena et al., 2019; Pareyson & Marchesi, 2009) |
| 510 | 8 year old female with club foot, ptosis, speech disturbance, intermittent exotropia, balance problem, weakness, lack of coordination, mixed receptive-expressive language disorder, fine motor impairment, sensory processing difficulty, global developmental delay |
arr[GRCh37] 18p11.32(13034_1324288) × 1, 18q23(73690111_78015180) × 1 |
18p11.32: 1.3 Mb deletion; 18q23: 4.3 Mb deletion |
CTDP1, TXNL4A, MBP | Ring chromosome 18 | This study; Monosomy of chr 18 and ring chr 18 with different breakpoints reported previously (Benini et al., 2012; Carter et al., 2015) |
| 411 | 4 year old male with autism spectrum disorder, global developmental delay, mixed receptive-expressive language disorder | arr[GRCh37] 21p11.2q22.3(10827533_48100155) × 2–3 |
21p11.2q22.3 Whole chromosome mosaic duplication |
Whole chromosome with many genes | Mosaic trisomy 21 | (Papavassiliou et al., 2015) |
| 193 | 15 year old female with developmental delay, moderate persistent asthma, eczema, allergic rhinitis, spells, spell of altered consciousness | arr[GRCh37] 21q22.3(44210786_48100155) × 1 |
21q22.3: 3.9 Mb deletion |
CSTB | 21q22.3 deletion | (Assenza et al., 2017; Ciocca et al., 2015; Poelmans et al., 2009) |
| 277 | 3 year old male with global developmental delay, seizure, postaxial polydactyly in both hands, self-injurious behavior, autism |
arr[GRCh37] 1p31.1(71987496_72370307) × 1, 22q11.21(18844632_21463730) × 1 mat |
1p31.1: 383 Kb deletion, 22q11.2: 2.6 Mb deletion |
TBX1, PRODH, COMT, SEPT5 | 22q11.2 deletion syndrome (LCR22A-D) | (McDonald-McGinn et al., 2015; Zinkstok et al., 2019) |
| 382 | 6 year old male with developmental delay, mixed receptive-expressive language disorder | arr[GRCh37] 22q11.21(18889490_21463730) × 1 |
22q11.21: 2.6 Mb deletion |
TBX1, PRODH, COMT, SEPT5 | 22q11.2 deletion syndrome (LCR22A-D) | |
| 291 | 2 year old male with global developmental delay | arr[GRCh37] 22q11.21(18640300_21462353) × 3 |
22q11.2: 2.8 Mb duplication |
TBX1 | 22q11.2 duplication syndrome | (Kylat, 2018; Portnoi, 2009; Vyas et al., 2019) |
| 147 | 2 year old male with global developmental delay, failure to thrive, hypotonia | arr[GRCh37] Xp21.1(31737146_31759752) × 0 |
Xp21.1: 23 Kb deletion |
DMD | Duchenne muscular dystrophy | (Juan-Mateu et al., 2015; Muntoni et al., 2003; Takeshima et al., 2010) |
| 416 | 6 year old male with accommodative esotropia, hypermetropia, speech disturbances | arr[GRCh37] Xp21.1(31764087_31864634) × 0 |
Xp21.1: 100.5 Kb deletion |
DMD | Duchenne/Becker muscular dystrophy | |
| 198 | 12 year old male with macrocephaly, epilepsy, autism | arr[GRCh37] Xq28(152662222_153524347) × 2 |
Xq28: 862 Kb duplication |
MECP2 | MECP2 duplication syndrome | (Lim et al., 2017; Ward et al., 2018) |
| 211 | 4 year old male with autism spectrum disorder, mixed receptive-expressive language disorder, global developmental delay, sensory processing difficulty, disturbance in sleep behavior, disruptive behavior, insomnia | arr[GRCh37] Xp22.31(6456940_8135053) × 0 |
Xp22.31: 1.7 Mb deletion |
STS, VCX3A, XLI | STS deficiency or X-linked ichthyosis (XLI) | (Ben Khelifa et al., 2013; Fernandes et al., 2010; Hand et al., 2015) |
| 308 | 2 year old male with global developmental delay, hypotonia and seizures | arr[GRCh37] Xp22.33q28(60814_155236712) × 2 |
Xp22.33–Xq28: whole chromosome duplication |
Whole chromosome with many genes | Klinefelter syndrome | (Crawford & Dearmun, 2017; Samango-Sprouse et al., 2020) |
| 321 | 4 year old male with autism spectrum disorder, global developmental delay | arr[GRCh37] Xp22.33q28(60814_155236712) × 2 |
Xp22.33–Xq28: whole chromosome duplication |
Whole chromosome with many genes | Klinefelter syndrome |
Patient identification number (ID), clinical information, International System for Human Cytogenetic Nomenclature (ISCN-2016) nomenclature, chromosome locations and size of alterations, genetic diagnosis and literature search results have been listed in the table. For patients with more than one CNV reported, the bolded CNV stands for the pathogenic/likely pathogenic CNV and the rest stand for Unknown Significance CNVs. See references in supplementary data