Background
Results
Global data
Pathogenic CNVs
Pathogenic + Likely pathogenic (n = 23) | Polymorphic CNVs (n = 134) |
---|---|
Gender | Gender |
Males 15 (65%) | Males 84 (63%) |
Females 8 (35%) | Females 50 (37%) |
ID | ID |
Syndromic 19 (83%) | Syndromic 74 (55%) |
Non-syndromic 4 (17%) | Non-syndromic 60 (45%) |
Borderline 1 (4%) | Borderline 8 (6%) |
Mild 15 (65%) | Mild 75 (56%) |
Moderate 6 (26%) | Moderate 30 (22%) |
Severe 0 (0%) | Severe 15 (11%) |
Profound 1 (4%) | Profound 6 (4%) |
History | History |
Sporadic 11 (48%) | Sporadic 54 (40%) |
Family history of ID 15 (65%) | Family history of ID 80 (60%) |
Co-morbidities | Co-morbidities |
Congenital anomalies 11 (48%) | Congenital anomalies 64 (48%) |
Epilepsy 2 (9%) | Epilepsy 19 (14%) |
Microcephaly 4 (17%) | Microcephaly 23 (17%) |
Macrocephaly 1 (4%) | Macrocephaly 13 (10%) |
Likely pathogenic CNVs
Patients | Gender | Alteration (Hg19) | Type | Size (Mb) | Genes | Key gene(s) involved | Associated syndrome | Phenotype overlap | Inheritance | Confirmation | Array platform | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|
R1 | Male | arr 1p36.23-p36.21(8,593,674-15,396,672)x1dn | del | 6.7 | 86 |
ANGPTL7, CASZ1, MAD2L2, RERE
| – | – | de novo | NP | 1 | – |
R2 | Male | arr 2p13.1-p13.3(70,894,906-74,986,518)x1dnc | del | 4 | 62 |
CYP26B1, EXOC6B
| – | – | de novo | NP | 1 | Wen J, 2013 |
R3 | Male | arr 3q22.1-q23(131,415,639-141,618,552)x1dn | del | 1.020 | 65 |
FOXL2
| BPES | Yes (eye features) | de novo | NP | 1 | – |
C1 | Male | arr 5p15.33-p15.32(204,849-5,014,883)x1 | del | 4.81 | 30 |
TERT [CTNND2 not involved]
| – | – | ND | NP | 2 | – |
R4 | Male | arr 6q25.3(156,012,754-158,804,494)x1dnc | del | 2.6 | 14 |
ARID1B
| Coffin-Siris syndrome | Yes | de novo | NP | 1 | Santen GW, 2013 |
C2 | Male | arr 7q11.23(72,721,760-74,140,846)x1 | del | 1.419 | 28 |
BAZ1B, STX1A, WBSCR22, ELN
| Williams-Beuren syndrome | Partially | ND | NP | 2 | – |
R5 | Female | arr 8p23.1(7,039,276-12,485,558)x1dn | del | 5.5 | 70 | SOX7, GATA4 | 8p23.1 deletion syndrome | Yes (cardiac) | de novo | NP | 1 | – |
C3 | Male | arr 11q24.2-q25(125,232,584-134,446,160)x1dn | del | 9.214 | 54 |
KIRREL3, ETS1, FLI1, KCNJ1, KCNJ5, RICS
| – | Partially | de novo | qPCR | 2 | – |
R6 | Female | arr 12q24.21-q24.22(115,505,500-117,441,683)x1dnc | del | 0.2 | 10 |
MED13L
| – | Yes | de novo | qPCR | 1 | Adegbola A, 2015 |
C4 | Male | arr 16p11.2(29,674,336-30,198,123)x1dn | del | 0.524 | 29 |
KCTD13
| 16p11.2 deletion syndrome | – | de novo | NP | 2 | – |
C5 | Male | arr 17q21.31(43,710,371-44,215,352)x1 | del | 0.505 | 8 |
CRHR1, MAPT, STH, and part of the KIAA1267 (KANSL1)
| 17q21.31 deletion syndrome (Koolen-De Vries syndrome) | – | ND | NP | 3 | – |
C6 | Male | arr 22q11.21(18,894,835-21,505,417)x1 | del | 2.611 | 59 |
TBX1
| 22q11 deletion syndrome | – | ND | NP | 2 | – |
C7 | Male | arr 22q13.3(49,513,903-51,178,264)x1 | del | 1.664 | 39 |
SHANK3
| 22q13.3 deletion syndrome (Phelan-McDermid syndrome) | Partially | ND | NP | 2 | – |
C8 | Male | arr 1q21.1q21.2(146,106,723-147,830,830)x3dn | dup | 1.7 | 17 |
HYDIN2, PRKAB2
| 1q21.1 duplication syndrome e | Partially | de novo | qPCR | 4 | – |
R7 | Male | arr 1q21.1(145,883,119-148,828,690)x3pat | dup | 2.5 | 23 |
HYDIN2, PRKAB2, GJA5
| 1q21.1 duplication syndrome e | Yes | paternal | NP | 1 | – |
R8 | Male | arr 12q24.21(116,408,736-116,704,303)x3dnc | dup | 0.3 | 2 |
MED13L
| – | Yes | de novo | qPCR | 1 | Adegbola A, 2015 |
C9 | Male | arr 13q12.12-q34(23,749,431-115,083,342)x2.15a | dup | 91.33 | ## |
–
| Trisomy 13 (mosaicism) | Yes | ND | Karyotyped | 2 | – |
C10 | Female | arr 15q11.2-q13.1(22880274–29,331,964)x3mat | dup | 6.45 | 111 |
CYF1P1, NIPA2, NIPA1, MKRN3, NDN, MAGEL2, SNURF/SNRPN, UBE3A GABRB3
| 15q11-q13 duplication syndromeb | Yes | maternal | NP | 2 | – |
C11 | Female | arr 16p13.11(15,034,010-16,199,882)x3 | dup | 1.166 | 11 |
NDE1
| 16p13.11 duplication syndrome e | – | ND | NP | 5 | – |
R9 | Male | arr 16p13.11(15,421,671-16,443,968)x3mat | dup | 1 | 19 |
NDE1
| 16p13.11 duplication syndrome e | Yes | maternal | NP | 1 | – |
R10 | Male | arr 16p13.11(15,484,180-16,308,344)x3mat | dup | 0.8 | 9 |
NDE1
| 16p13.11 duplication syndrome e | Yes | maternal | NP | 1 | – |
C12 | Male | arr 21q11.2-q22.11(14,417,523-34,894,625)x3 | dup | 20.47 | 110 |
DSCR1, DSCR2, DSCR3, DSCR4, APP
| – | No | ND | NP | 2 | – |
R11 | Male | arr Xp11.22(53,569,653-53,769,748)x2mat | dup | 0.2 | 3 |
HUWE1
| – | Yes | maternal | qPCR | 1 | – |
R12 | Male | arr Xq28(152,348,378-155,228,013)x2dn | dup | 2.8 | 78 |
MECP2
| MECP2 duplication syndrome | Yes | de novo | NP | 1 | – |
R13 | Male | arr Xq28(153,130,545-153,602,293)x2mat | dup | 0.5 | 16 |
MECP2
| MECP2 duplication syndrome | Yes | maternal | NP | 1 | – |
R14 | Male | arr 9q34.13-q34.3(135,767,911-141,153,431)x3dn | dup | 5.516 | 135 |
EHMT1, RXRA, GRIN1, UAP1L1
| 9q34 duplication syndrome | Partially | de novo | NP | 1 | – |
arr 14q32.31-q32.33(102,959,110-104,578,612)x3dn | dup | 1.620 | 22 |
MARK3, KLC1, EIF5
| – | – | de novo | NP | 1 | – | ||
arr 14q32.33(105,104,831-106,531,339)x3dn | dup | 1.427 | 24 | – | – | de novo | NP | 1 | – |
2q11.2-q12.2 deletion
17p11.2 deletions
20q13.12-q13.13 deletions
1p22.1p21.3 duplications
9q33.2-q33.3 triplication
Xq24 duplication
Xq26.3 duplication
CNVs of unknown significance
Discussion
NDDs associated pathways: old and new genes
Transcriptional factors/cell cycle regulators/DNA repair proteins
Chromatin modifiers/chromatin remodeling proteins
Ubiquitin signaling
Cytoskeleton regulation and organization, cell shape and motility
Intracellular vesicular trafficking and exocytosis
Signaling mediators/transducers/ receptor activity/transmembrane proteins
Conclusion
Subjects and methods
Subjects
Patients | Gender | Alteration (Hg19) | Type | Size (Kb) | Genes | Relevant genes involved | Confirmation | Inheritance | DGV controls | DECIPHER | Array platform | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|
C13 | Male | arr 1q43-q44(240,043,427-249,233,096)x1dn f | del | 3.7 | 18 |
AKT3
| qPCR | de novod | No | 250,152, 250,915 (smaller) | 1 | Lopes F, et al., 2019 |
R15 | Female | arr 1q43-q44(243,552,007-243,738,675)x1dn f | del | 0.19 | 2 |
AKT3
| qPCR | de novod |
No
| 252,432 (smaller) | 2 | Lopes F, et al., 2019 |
C14 | Male | arr 1q43q44(243,592,147-243,749,968)x1pat f | del | 0.16 | 2 |
AKT3
| qPCR | paternal |
No
| 252,432 (smaller) | 1 | Lopes F, et al., 2019 |
R16 | Female | arr 2q11.2-q12.2(101,756,265-106,265,018)x1dn | del | 4500 | 24 |
MAP4K4, FHL2, POU3F3, CNOT11
| qPCR | de novo | No | 251,756 | 2 | – |
R17, R18e | Male, Female | arr 7q33(133,176,651-135,252,871)x1mat f | del | 2076 | 23 |
AGBL3, CNOT4, CALD1, EXOC4
| qPCR | maternala | No | 256,036 | 2 | Lopes F, et al., 2018 |
R19 | Female | arr 10q26.3(131,374,701-132,030,468)x1dn | del | 600 | 3 |
EBF3
| qPCR | de novo | 3/6564b | No | 2 | Lopes F et al., 2017 |
C15 | Male | arr 17p11.2(16,757,564-17,178,161)x1mat | del | 420 | 5 |
COPS3
| NP | maternala | No | No | 3 | – |
arr 17p11.2(18,478,816-21,255,056)x1mat | del | 2770 | 36 |
EPN2, RNF112, ULK2, ALDH3A2, AKAP10, B9D1
| NP | maternala | No | 340,692 (smaller) | – | |||
R20 | Female | arr 20q13.12-q13.13(43,283,820-48,850,844)x1dn | del | 5500 | 88 |
KCNB1, PIGT, CTSA, SLC2A10, ARFGEF2
| NP | de novo | No | 309 | 2 | – |
C16 | Female | arr 1p22.1p21.3(92,227,986-98,689,243)x3mat | dup | 6461 | 44 |
FAM69A, TGFBR3, GLMN, EVI5, RPL5, MTF2, DR1, ABCA4, ABCD3, CNN3, PTBP2, DPYD
| qPCR | maternala | No | 318,358 | 1 | – |
C17,C18e | Male, Male | arr 7q33(134,598,205-134,815,177)x3mat f | dup | 216 | 2 |
CALD1, AGBL3
| qPCR | maternala | No | No | 1 | Lopes F, et al., 2018 |
R21 | Female | arr 9q33.2-q33.3(123,525,064-127,187,619)x4dn | tri | 3600 | 52 |
CRB2, LHX2, LHX6, DENND1A, STRBP, RAB14, GSN, PSMB7, ZBTB26
| qPCR | de novo | No | No | 2 | – |
C19 | Female | arr 9q34.3(140540819–140,659,057)×3mat | dup | 0.118 | 2 |
EHMT1
| NP | maternal | 1/2504 (smaller) | No | 1 | – |
R22, R23e | Male, Male | arr Xq24(119,592,606-119,904,981)x2mat | dupc | 300 | 4 |
CUL4B, LAMP2, C1GALT1C1, MCTS1
| qPCR | maternal | No | No | 2 | – |
C20 | Male | arr Xq26.3(135,293,144-135,863,290)x2mat | dup | 570 | 9 |
ARHGEF6, CD40LG, BRS3, MAP7D3
| qPCR | maternal | No | No | 3 | – |