Table 2.
Pathogenic and likely pathogenic variants identified in the solved patients. For the genetic diagnosis, MIM numbers are provided when available.
| Genetic diagnosis (MIM #) | Genomic coordinates (CNV type) | Size | Class | Rationale for the classification | Phenotype (gender) | Inher |
|---|---|---|---|---|---|---|
| 1p36.33-p36.32 duplication | chr1:835601-3648438 | 2.8–3.6 | P | ClinVar and DECIPHER with similar CNV classified as P/LP | GDD/ID + epi (F) | Inh |
| 1p21.3-p13.3 deletion | chr1:98429416-111608309 | 13.2–13.3 | P | Known variant/syndrome | GDD/ID + epi (M) | NA |
| 2q13 deletion | chr2:109737782-114719444 | 1.7–2.2 | P | Known variant/syndrome | GDD/ID_isol (M) | DN |
| 2q22.3-q23.3 duplication | chr2:144709544-154452355 | 9.7–10 | P | Known variant/syndrome | GDD/ID_synd (M) | DN |
| 3q26.32 deletion | chr3:176720110-177692976 | 0.97–1.2 | P | TBL1XR1 known GDD gene | GDD/ID_isol (M) | DN |
| 3q29 deletion syndrome | chr3:195769570-197332976 | 1.6–1.8 | P | Known variant/syndrome | GDD/ID + micro/macro (M) | DN |
| 4q13.2-q13.3 deletion | chr4:68155831-73330955 | 5.2–5.4 | P | ClinVar and literature with similar CNV classified as P/LP | GDD/ID_synd (F) | NA |
| 7q22.1 deletion | chr7:101668049-103143668 | 1.5–1.6 | P | RELN known GDD/epilepsy gene | GDD/ID + epi (F) | NA |
| AUTS2 syndrome (MIM #615834) | chr7:67767963-69320956 (dup) | 1.6–1.7 | P | Known variant/syndrome | GDD/ID_isol (M) | DN |
| chr7:69564262-695927 (del) | 0.03–0.06 | P | ASD_isol (M) | DN | ||
| 7q11.23 duplication syndrome | chr7:72221649-74339044 | 2.1–3.2 | P | Known variant/syndrome | GDD/ID_isol (F) | NA |
| chr7:72745047-74138460 | 1.4–2.1 | P | GDD/ID_synd (F) | DN | ||
| 10q11.22-q11.23 deletion | chr10:49392896-52362158 | 3.0–4.0 | LP | ClinVar and DECIPHER with similar CNV classified as P/LP | GDD/ID_isol (M) | NA |
| 11p15.5 deletion | chr11:205827-697426 | 0.49–0.74 | P | Possible candidate genes: DEAF1, DRD4 | ASD_isol (F) | DN |
| Lamb–Shaffer syndrome (MIM #616803) | chr12:23916595-24134081 (del) | 0.22–0.25 | P | Known variant/syndrome | GDD/ID_synd (F) | DN |
| 12q21.2-q21.31 duplication | chr12:79831049-85693154 | 5.9–6.03 | LP | ClinVar and DECIPHER with similar CNV classified as P/LP | GDD/ID_isol (M) | NA |
| FGF14 deletion (MIM #609307) | chr13:102992332-103117739 | 0.13–0.15 | LP | Known gene | GDD/ID_isol (F) | DN |
| 15q11-q13 duplication syndrome | chr15:22822019-28513165 (x3 individuals) | 5.7–29 | P | Known variant/syndrome | GDD/ID_isol (2F, 1M) | DN |
| (MIM #608636) | chr15:22822019-32438943 | 5.7–29 | P | Known variant/syndrome | GDD/ID_isol (F) | DN |
| Angelman syndrome (MIM #105830) | chr15:23717628-28513165 (del) | 4.8–6.1 | P | Known variant/syndrome | GDD/ID_synd (M) | NA |
| Prader–Willi syndrome (MIM #176270) | chr15:23717628-28513165 (del) | 4.8–6.1 | P | Known variant/syndrome | Other_isol (M) | NA |
| 15q26 microdeletion | chr15:94995432-993443687 | 4.4–4.5 | P | Known variant/syndrome | GDD/ID_synd (F) | DN |
| Smith Magenis syndrome (MIM #182290) | chr17:16814853-20079020 (del) | 0.50–0.53 | P | Known variant/syndrome | GDD/ID_isol (M) | NA |
| 17q12 recurrent deletion syndrome (MIM #614527) | chr17:34816424-36207539 | 1.4–2.0 | P | Known variant/syndrome | GDD/ID_isol (F) | NA |
| Koolen de Vries syndrome (MIM #610443) | chr17:43713616-44275738 (del) | 0.6–1.30 | P | Known variant/syndrome | GDD/ID_synd (M) | NA |
| 17p13.3 duplication syndrome (MIM #613215) | chr17:78346-347175 | 3.4–3.5 | P | Known variant/syndrome | GDD/ID_synd (F) | DN |
| 18q12.1-q12.3 deletion | chr18:32241257-38294860 | 6.1–6.2 | P | Known variant/syndrome (CELF4 candidate gene) | GDD/ID_isol (F) | DN |
| 18q- syndrome (MIM #601808) | chr18:68240572-76669641 (del) | 8.4–8.6 | P | Known variant/syndrome | GDD/ID_synd (M) | NA |
| chr18:72343121-78013620 (del) | 5.7–5.8 | Known variant/syndrome | GDD/ID_synd (M) | DN | ||
| 22q11.21 duplication | chr22:20734765-21417548 | 0.68–1.6 | P | Known variant/syndrome | ASD_isol (M) | DN |
| 22q11.2 duplication syndrome | chr22:18919528-21349219 | 2.5–3.2 | P | Known variant/syndrome | GDD/ID_isol (F) | DN |
| 22q11.2 deletion syndrome (MIM #18840) | chr22:18919528-21417548 | 2.5–3.2 | P | Known variant/syndrome | GDD/ID_isol (F); GDD/ID_synd (M); Other_isol (M) | DN |
| 22q11.2 microdeletion (MIM #611867) | chr22:21798705-22951375 | 1.2–1.7 | P | Known variant/syndrome | GDD/ID_synd (F) | NA |
| Phelan McDermid syndrome (MIM #606232) | chr22:51137326-51178150 (del) | 0.04–0.17 | P | Known variant/syndrome | GDD/ID + epi (F); GDD/ID_isol (M) | NA; DN |
| Xq28 duplication syndrome (MIM #300815) | chrx:153578515-153783185 | 0.20–0.26 | P | Known variant/syndrome | GDD/ID + micro/macro (M) | Inh |
| Xq25 microduplication syndrome | chrX:123002811-123237762 | 0.24–0.34 | P | Known variant/syndrome | GDD/ID_isol (M) | NA |
| Partial duplication of IL1RAPL1 (MIM #300143) | chrX:29595176-30070288 | 0.48–0.52 | LP | Known gene and mechanism | GDD/ID_synd (M) | NA |
| Xp22.32-22.2 deletion (MIM #308100, #308700, #300000) | chrX:5748782-10477366 | 4.7–4.8 | P | Known variant/syndrome | GDD/ID_synd (F) | DN |
| ATRX syndrome (MIM #301040) | chrX:76411307-76972336 (del) | 0.56–0.71 | P | Known variant/syndrome | ASD_isol (M) | DN |
| Unbalanced product of parental translocations/Chromosomal rearrangement | der(12)t(7;12)(p22.3p13.33) | – | P | ASD_isol (F) | – | |
| der(18)t(9;18)(p23;p11.31) | – | P | GDD/ID_isol (F) | – | ||
| Rearrangement chr18 | – | P | GDD/ID_isol (M) | – | ||
| Complex rearrangement chr9 | – | P | GDD/ID_isol (F) | – | ||
| Complex rearrangement chr1 | – | P | GDD/ID_synd (M) | – |
Genomic coordinates correspond to hg19. For the type of CNV del deletion, dup duplication. Size includes the minimum and maximum estimated size in Mb; NA not available; For the inheritance, DN de novo, Inh inherited, NA not available. For the variant class, LP likely pathogenic and P pathogenic. For the phenotype: ASD Autism spectrum disorder, GDD/ID Global developmental delay/intellectual disability, Other NDDs Other neurodevelopmental disorders, epi epilepsy, isol isolated forms micro/macro micro/macrocephaly, synd syndromic, F female, M male.