Array-comparative genomic hybridization results in clinically affected cases with apparently balanced chromosomal rearrangements

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)

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
1^a	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
2^a	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	–	–	–
3^a	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	–	–	–
4^a	M-4	PSMR; drug therapy due to convulsion; facial dysmorphism; pes planus	46,XY,t(2;10)(q33.2;p12.32)	normal	–	–	–
5^a	F-7	PSMR; hypotonia; central obesity; childhood polyphagia	46,XX,t(6;9)(q25.1;q32)	normal	–	–	–
6^b	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	–		–
7^b	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	–	–	–
8^b	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	–	–	–
9^b	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
10^a	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
11^b	M-13	ID; undescended testicle; advanced bone age; obesity; agitation; fragile X test normal	46,XY,parinv(12)(p13.3q13.1)pat	normal	–	–	–
12^b	M-3	consanguineous marriage; PSMR; growth retardation; microcephaly; facial dysmorphism; clinodactyly; joint hypermobility	46,XY,inv(12)(p11q14)mat	normal	–	–	–
13^b	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
14^a	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
15^a	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
16^a	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
17^a	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	–	–	–
19^a	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	–	–	–
20^a	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
21^a	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

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
22^a	24/CVS	NT (5 mm)	46,XX,t(2;4)(p23;q31.1)	normal	–	–	–
23^a	21/AC	abdominal cysts; polyhydramnios	46,XY,t(10;16)(q23.2;q13)	10q23.1(86441275-87680071)x1	1.2 Mb	loss	de novo
24^a	24/AC	dilated intestine; EIF	46,XX,t(7;12)(q36;q15)	normal	–	–	–
25^a	17/AC	CPCs; fetal intracranial cysts	46,XY,t(2;3)(q31.2;q27.32)	normal	–	–	–
26^a	19/AC	CPCs	46,XX,t(3;16)(p21.3q11)	16p11.2(28220816-33816801)x3	5.5 Mb	gain	maternal
27^a	23/AC	SUA; HEB; increased cardiothoracic ration	46,XY,t(5;13)(q15;q22)	normal	–	–	–
28^a	20/AC	bilateral ventriculomegaly; hydrochephalus	46,XX,t(8;16)(q24.1;q12.1)	normal	–	–	–
29^b	24/AC	asymmetric ventriculomegaly	46,XY,t(15;17)(q24.1;q21.3)pat	normal	–	–	–
30^b	22/FBS	bilateral pes equinovarus; amniotic band sequence	46,XY,t(11;15)(q13.3;q25)pat	normal	–	–	–
Inversions
31^b	23/FBS	situs inversus totalis, CHD	46,XY,inv(12)(p11.23q15)mat	normal	–	–	–
32^b	22/AC	anhydramnios; laryngeal atresia; bilateral renal agenesis; SUA; absence/hypoplasia of lower extremities; ambiguous genitalia	46,XX,inv(7)(q11.2q32)mat	normal	–	–	–
33^b	24/FBS	ascites; polyhydramnios; IUMF; increased cardiothoracic ratio; thick placenta	46,XX,inv(6)(q21.2q26)pat	normal	–	–	–
Complex Chromosome Rearrangements
34^a	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	–	–	–

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Array-comparative genomic hybridization results in clinically affected cases with apparently balanced chromosomal rearrangements

Article Category: Original article

Publié en ligne: 23 mars 2021

Pages: 25 - 34

DOI: https://doi.org/10.2478/bjmg-2020-0026

Mots clésApparently balanced structural chromosomal abnormalities (ABCRs), Array-comparative genomic hybridization (aCGH), Chromosomal microarray (CMA), Cryptic genomic imbalances, Fetal ultrasound findings

© 2020 Satkin NB, Karaman B, Ergin S, Kayserili H, Kalelioglu IH, Has R, Yuksel A, Basaran S, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Comparison with the previous reports for postnatal de novo patients.

Clinical findings, karyotype and chromosomal microarray results for the postnatal patients.

Ultrasonography findings, karyotype and chromosomal microarray results for the prenatal patients.

Mots clés
Apparently balanced structural chromosomal abnormalities (ABCRs), Array-comparative genomic hybridization (aCGH), Chromosomal microarray (CMA), Cryptic genomic imbalances, Fetal ultrasound findings