Table 1
Clinical findings, karyotype and chromosomal microarray results for the postnatal patients.
| # | Sex- Age | Clinical Details | Initial Karyotype | CMA Result (GRCh37/hg19] | Size | Type of Anomaly (gain/loss) | Parental Origin of Imbalance |
|---|---|---|---|---|---|---|---|
| Translocations | |||||||
| 1a | M-4 | consanguineous marriage; stereotypic hand movements, PSMR; short eye contact duration; pathology in brain MRI; ASD | 46,XY,t(4;10)(q34.2;q26.2) | 10q26.3 (130669231-135534747)x3 | 4.8 Mb | gain | de novo |
| 2a | M-13 | minimal nonspecific ID; hypo-glycemia; cryptorchidism; facial dysmorphism; short neck; hypo-myelinization and subarachnoid enlargement in cranial CT | 46,XY,t(4;10)(q25;q22.1) | normal | – | – | – |
| 3a | M-6 | PSMR; anal stenosis; bilateral inguinal hernia; facial dysmorphism; macrocephaly; short fingers and clinodactyly on the fifth finger | 46,XY,t(5;17)(q12.2;q21.33) | normal | – | – | – |
| 4a | M-4 | PSMR; drug therapy due to convulsion; facial dysmorphism; pes planus | 46,XY,t(2;10)(q33.2;p12.32) | normal | – | – | – |
| 5a | F-7 | PSMR; hypotonia; central obesity; childhood polyphagia | 46,XX,t(6;9)(q25.1;q32) | normal | – | – | – |
| 6b | M-11 | consanguineous marriage; ID; hyperactivity; poor eye contact, repetitive speech; family history of MR (paternal side); fragile X test normal | 46,XY,t(9;10)(p22;q24)pat | normal | – | – | |
| 7b | M-13 | consanguineous marriage; mild ID; brother and maternal aunt’s daughter affected; microphthalmia; severe PSMR; muscle atrophy; microcephaly; bilateral hydronephrosis; facial dysmorphism | 46,XY,t(6;19)(p11;p13.2)mat | normal | – | – | – |
| 8b | F-9 | consanguineous marriage; microcephaly; facial dysmorphism; clinodactyly; cranial CT consistent with Lissencephaly type 1 | 46,XX,t(3;4)(p22;q26)mat (negative FISH result for Smith- Magenis-Dieker Probe) | normal | – | – | – |
| 9b | M-1 | consanguineous marriage; facial dysmorphism; CHD; right kidney agenesis, left kidney size increase; undescended testicle; anal atresia | 46,XY,t(8;22)(p11.2;q22)mat | normal | – | – | – |
| Inversions | |||||||
| 10a | F-7 | neuromotor retardation; seizures; growth retardation; microcephaly; facial dysmorphism; clinodactyly; pathology in brain MRI | 46,XX,inv(1)(q25.1q32.2) | 1q23.3q24.2(161969134-169579696)x1 | 7.6 Mb | loss | de novo |
| 11b | M-13 | ID; undescended testicle; advanced bone age; obesity; agitation; fragile X test normal | 46,XY,parinv(12)(p13.3q13.1)pat | normal | – | – | – |
| 12b | M-3 | consanguineous marriage; PSMR; growth retardation; microcephaly; facial dysmorphism; clinodactyly; joint hypermobility | 46,XY,inv(12)(p11q14)mat | normal | – | – | – |
| 13b | M-5 | consanguineous marriage; pectus excavates; pulmonary stenosis; cryptorchidism, micropenis; lytic bone lesions; mutation negative in RAF1, KRAS, SHOC2 genes | 46,XY,parinv(12)(q21.2q24.1)mat | normal | – | – | – |
| Complex Chromosome Rearrangements | |||||||
| 14a | M-4 | PSMR; hypotonia; microcephaly; syndactyly; lack of eye contact | 46,XY,t(8;13)(q24.13;q21.2), ins(2)(p16.2q33.2q22.2) | 2q36.1q36.3(225194399-228263782)x1 | 3.0 Mb | loss | de novo |
| 15a | M-9 | PSMR; alopecia; hyperpigmentation; facial dysmorphism; bilateral cubitus valgus; accessory nipple on bilateral nipple line; tracheostomy | 46,XY,inv(3)(p13p25)t(11;18) (p13.5;q12.2) | 4q13.3(71013108-72174576)x1 4q13.3q21.2(73373677-76306815)x1 | 1.1 Mb 2.9 Mb | loss loss | de novo |
| 16a | M-1 | bilateral aniridia; cryptorchidism; micropenis; heart murmur; hypertonia of the lower extremities | 46,XY,t(3;15;21)(p13;q21.1; q22.3),t(4;16)(q31;p31.1) | 11p14.13(30031595-33045209)x1 | 2.5 Mb | loss | de novo |
| 17a | F-3 | PSMR; microcephaly; dystrophinopathy; myogenic EMG findings; walking difficulties | 46,X,t(X;13;17)(p21;q13;q22) | normal | – | – | – |
| 18 | M-3 | CHD; negative FISH result for DiGeorge syndrome | 46,XY,der(3)(15qter→15q22.3: :3p11.2→3qter)der(15)(15pter→ 15q22.3::3p26→3p11.2: :3p26→3pter) | normal | – | – | – |
| 19a | F-13 | mild ID; dystrophinopathy; Gowers’ sign; pektus ekskavatum; minimal facial dysmorphism; normal MLPA result | 46,X,t(X;8;14)(8qter→8q11: :Xp21→Xqter)(Xpter→Xp21: :8p21.1→8q11::14q13) | normal | – | – | – |
| 20a | M-4 | consanguineous marriage; neuromotor retardation; mild ID; facial dysmorphism; brachycephaly; hypoplastic scrotum | 46,XY,t(1;18)(q32.1;q23),t(5;12) (p14.2;q21.2) | 5q13.3-q14.1(74571645-77654540)x1 5q14.3(90604937-92259476)x1 5q15(93668778-95921236)x1 9p23p22.3(14030668-16317401)x1 | 2.4 Mb 1.6 Mb 1.9 Mb 2.3 Mb | loss loss loss loss | de novo |
| 21a | F-2 | facial dysmorphism; short neck; soft, dry skin; clinodactyly; bilateral clubfoot, talipes echi- novarus; hypoplastic clitoris; tooth grinding; multiple renal stones; partial ACC; normal MLPA result | 46,XX,t(11;13;18)(13pter→ 13q22::11p13→11pter; 13qter→13q22::11p13→11q24: :18q21→18qter;18pter→18q21: :11q24→11qter) | 11p14.3(22454510-246887178)x1 18q21.2q21.32(48286848-58934492)x1 21q11.2q21.1(15598880-18332856)x1 | 2.2 Mb 10.6 Mb 2.7 Mb | loss loss loss | de novo |
[i] #: case number; CMA: chromosomal microarray; PSMR: psychomotor retardation; MRI: magnetic resonance imaging; ASD: atrial septal defect; ID: intellectual disability; CHD: congenital heart defect; FISH: fluorescent in situ hybridization; MLPA: multiplex ligation-dependent probe amplification; ACC: agenesis of corpus callosum.
aDe novo rearrangement.
b Familial rearrangement.
Table 2
Ultrasonography findings, karyotype and chromosomal microarray results for the prenatal patients.
| # | Weeks’ Gestation/ Invasive Procedure | USG Findings | Initial Karyotype | CMA Result (GRCh37/hg19] | Size | Type of Anomaly (gain/loss) | Parental Origin of Imbalance |
|---|---|---|---|---|---|---|---|
| Translocations | |||||||
| 22a | 24/CVS | NT (5 mm) | 46,XX,t(2;4)(p23;q31.1) | normal | – | – | – |
| 23a | 21/AC | abdominal cysts; polyhydramnios | 46,XY,t(10;16)(q23.2;q13) | 10q23.1(86441275-87680071)x1 | 1.2 Mb | loss | de novo |
| 24a | 24/AC | dilated intestine; EIF | 46,XX,t(7;12)(q36;q15) | normal | – | – | – |
| 25a | 17/AC | CPCs; fetal intracranial cysts | 46,XY,t(2;3)(q31.2;q27.32) | normal | – | – | – |
| 26a | 19/AC | CPCs | 46,XX,t(3;16)(p21.3q11) | 16p11.2(28220816-33816801)x3 | 5.5 Mb | gain | maternal |
| 27a | 23/AC | SUA; HEB; increased cardiothoracic ration | 46,XY,t(5;13)(q15;q22) | normal | – | – | – |
| 28a | 20/AC | bilateral ventriculomegaly; hydrochephalus | 46,XX,t(8;16)(q24.1;q12.1) | normal | – | – | – |
| 29b | 24/AC | asymmetric ventriculomegaly | 46,XY,t(15;17)(q24.1;q21.3)pat | normal | – | – | – |
| 30b | 22/FBS | bilateral pes equinovarus; amniotic band sequence | 46,XY,t(11;15)(q13.3;q25)pat | normal | – | – | – |
| Inversions | |||||||
| 31b | 23/FBS | situs inversus totalis, CHD | 46,XY,inv(12)(p11.23q15)mat | normal | – | – | – |
| 32b | 22/AC | anhydramnios; laryngeal atresia; bilateral renal agenesis; SUA; absence/hypoplasia of lower extremities; ambiguous genitalia | 46,XX,inv(7)(q11.2q32)mat | normal | – | – | – |
| 33b | 24/FBS | ascites; polyhydramnios; IUMF; increased cardiothoracic ratio; thick placenta | 46,XX,inv(6)(q21.2q26)pat | normal | – | – | – |
| Complex Chromosome Rearrangements | |||||||
| 34a | 23/FBS | IUGR; ambiguous genitalia; micropenis; hand and foot deformities; ASD | 46,XY,t(1;9;11)(1pter→1q43: :9p22.2→9pter;11pter→ 11p11.22::9p21→9qter) | normal | – | – | – |
[i] USG: ultrasonography; CMA: chromosomal microarray; CVS: chorionic villus sampling; NT: nuchal translucency; AC: amniocentesis; EIF: echogenic intracardiac focus; CPCs: choroid plexus cysts; SUA: single umbilical artery; HEB: hyperechogenic bowel; FBS: fetal blood sampling; CHD: congenital heart failure; IUMF: in utero mort fetalis; IUGR: intrauterine growth restriction; ASD: autism spectrum disorder.
aDe novo rearrangment.
b Familial rearrangement.
Table 3
Comparison with the previous reports for postnatal de novo patients.
| Study | Array Platform | Translocation | Inversion | CCRs | Total | Imbalances at the Breakpoint | Imbalances at Different Breakpoint Regions |
|---|---|---|---|---|---|---|---|
| [13] | 1 Mb BAC | 5/8 (62.5) | – | 0/2 (0.0) | 5/10 (50.0) | 2/10 (20.0) | 3/10 (30.0) |
| [11] | Agilent 44K or 244k | 11/27 (40.0) | – | 12/13 (92.3) | 23/40 (57.5) | 16/40 (40.0) | 7/40 (17.5) |
| [37] | Agilent Genomics 244k/2600, BAC, Spectral | 4/9 (44.4) | – | – | 4/9 (44.4) | 1/9 (11.1) | 3/9 (33.3) |
| [34]a | Whole Genome Tilepath 30k | 4/11 (36.3) | – | 1/2 (50.0) | 5/13 (38.4) | 4/13 (30.7) | 1/13 (7.7) |
| [5] | Cytochip Bluegnome 1 Mb | 2/6 (33.2) | – | – | 2/6 (33.2) | 1/6 (16.6) | 1/6 (16.6) |
| [14] | Agilent 44K or 244k | 8/21 (38.1) | 4/7 (57.1) | 4/5 (80.0) | 16/33 (48.5) | 9/33 (27.3) | 7/33 (21.2) |
| [16]a | Affymetrix GeneChip 250k | 3/3 (100.0) | 2/2 (100.0) | – | 5/5 (100.0) | 2/5 (40.0) | 3/5 (60.0) |
| [12]a | 32250k k BAC, Affymetrix 105k/244k Agilent, | 11/40 (27.5) | 0/6 (0.0) | 7/8 (87.5) | 18/54 (33.3) | 11/54 (20.3) | 7/54 (13.0) |
| [15]a | 370k, 370-Duo Illumina | 2/5 (40.0) | 2/4 (50.0) | – | 4/9 (44.4) | 2/9 (22.2) | 2/9 (22.2) |
| [17] | 135k NimbleGen CGX-3 | 3/7 (43.0) | 1/4 (25.0) | – | 4/11 (36.4) | 3/11 (27.3) | 1/11 (9.1) |
| [38] | SNP 6.0/750k Affymetrix | 1/11 (9.0) | 0/3 (0.0) | 1/1 (100.0) | 3/15 (20.0) | 1/15 (6.7) | 2/15 (13.3) |
| This study | 1.4M NimbleGen CGX-3/ 180k Agilent | 1/5 (20.0) | 1/1 (100.0) | 5/8 (62.5) | 7/14 (50.0) | 2/14 (14.3) | 5/14 (35.7) |
| Total | 55/153 (35.9) | 10/27 (37.0) | 29/39 (74.4) | 96/219 (43.8) | 54/219 (24.6) | 42/219 (19.2) |
[i] CCRs: complex chromosome rearrangements; BAC: bacterial artificial chromosome.
Manufacturers’ locations. BAC: in-house methods; Agilent Technologies Inc.: Santa Clara, CA, USA; Spectral Genomics Co.: Houston, TX, USA; Whole Genome Tilepath: in-house methods; BlueGnome Ltd.: Cambridge, Cambridgeshire, UK; Affymetrix, Inc.: Santa Clara, CA, USA; Illumina Inc.: San Diego, CA, USA; Roche NimbleGen, Inc.: Madison, WI, USA.
a Unknown parental origins for karyotype result of the reported cases were excluded.