Table 3.
Pathogenic chromosome abnormalities detected in the 225 patient heterotaxy cohort. abd., abdominal; abnl/abnls., abnormal/abnormalities; ASD, atrial septal defect; AVC, atrioventricular canal; bilat., bilateral; CAVC, complete atrioventricular canal; d-TGA, dextro-transposition of the great arteries; DD, developmental delay; dil., dilated; DILV, double inlet right ventricle; DORV, double outlet right ventricle; HLHS, hypoplastic left heart syndrome; IVC, inferior vena cava; l-TGA, levo-transposition of the great arteries; Lt., left; LV, left ventricle; PA, pulmonary atresia; PAPVR, partial anomalous pulmonary venous return; PDA, patent ductus arteriosus; PS, pulmonic stenosis, Rt., right; RA, right atrium; RV, right ventricle; SI, situs inversus; SVC, superior vena cava; TAPVR, total anomalous pulmonary venous return; UPD, uniparental disomy; VSD, ventricular septal defect.
| patient | gender | type | platforma | cytogenetic findings (breakpoints)b |
inheritance/phenotype | |||
|---|---|---|---|---|---|---|---|---|
| illumina SNP array | illumina size | agilent oligo array | agilent size | |||||
| 1 | M | gain | oligo | not analysed | not analysed | arr 9q33.2-q33.3(125204518-140138901)x3 | 14.9 Mb | sporadic/l-TGA, PA, ASD, VSD |
| 2 | M | unbalanced translocation/complex rearrangement | oligo | not analysed | not analysed | arr 5q15q35.3(94068223-176886171)x3 arr 9p24.1p23(8442856-12223883)x1 |
82 Mb, 3.8 Mb | familial/d-TGA, CAVC, VSD, ASD, asplenia |
| 3 | M | loss | 1 M, oligo | arr 22q11.1q11.21(15815765-16422571)x1 | 600 kb | arr 22q11.1q11.21(15815765-16422571)x1 | 600 kb | sporadic/situs ambiguus, abd. SI, VSD, DORV, PS, PA, SVC abnls., asplenia, renal abnls., pulmonary isomerism, heart malrotation, hypoplastic pulmonary artery, central gallbladder, pancreas rotated to Rt., stomach rotated to Lt., hypoplastic multicystic Rt. kidney, undescended Lt. testicle, absent Rt. testicle. |
| 4 | M | gain; UPD | 1 M | arr 2p12p11.2(82350453-84912738)x3, arr 11p14.2q13.3(26301682-70604313)x2 hmz |
2.6 Mb, 44.3 Mb | not analysed | not analysed | familial/oligohydramnios, hypoplastic lungs; ASD, PAPVR, DORV, CAVC, dextrocardia; UPD leads to homozygous BBS1 nonsense mutation |
| 5 | F | mosaic gain and loss | 1 M, oligo | arr 7p22.3p21.3(34332-12922987)x1-2 arr 7p21.3p15.1(12925517-28332937)x1-2 hmz arr 7p15.1p12.3(28333319-48346413)x1-2 arr 7p12.1(48346704-48898843)x2-3 arr 7p12.1p11.2(51513509-56362278)x2-3 |
12.9 Mb, 15.4 Mb, 20 Mb, 552.1 kb, 2.6 Mb | arr 7p22.3p12.3(136551-48338627)x1 arr 7p11.2(53925715-56351979)x3 |
48.2 Mb, 2.4 Mb | unknown/SI; PDA; Kartagener's: immotile cilia by nasal biopsy; consanguinity (parents are first cousins) |
| 6 | F | loss | oligo | not analysed | not analysed | arr 2p25.3(3274169-3431910)x1 arr 22q11.2(17020267-19761174)x1 |
157.7 kb, 2.7 Mb | unknown/Rt. aortic arch, VSD; abd. SI; gut malrotation |
| 7 | M | loss | 1 M, oligo | arr 8p23.3p21.2(146703-25298793)x1 | 25.2 Mb | arr 8p23.3p21.2(151470-25293991)x1 | 25.1 Mb | sporadic/DORV, ASD, VSD, PS, polysplenia, mitral atresia, duplicated IVC, midline pancreas, hypoplastic scrotum, microcephaly (FOC 45 cm), bilat. medial ulegyria of frontal hemispheres, organomegaly (liver, spleen, kidneys more than 95% for age) |
| 8 | M | mosaic monosomy 21 | 1 M, oligo | arr 21q11.2q22.3(13989691-46942324)x1-2 | 33 Mb | arr 21q11.2q22.3(13971999-46914745)x1 | 32.9 Mb | sporadic/dextrocardia, SVC abnls., hypoplastic Rt. thumb, chordee |
| 9 | M | complex rearrangement | 1 M, oligo | arr 2q35(216859560-217354800)x3 arr 18p11.32p11.31(99027-6681691)x1 arr 18p11.31p11.21(6683107-15400816)x3 |
494.2 kb, 6.6 Mb, 8.7 Mb | arr 2q35(216852776-217347523)x3 arr 18p11.32p11.31(121700-6596548)x1 arr 18p11.31p11.21(6684807-14969496)x3 |
494.7 kb, 6.5 Mb, 8.3 Mb | sporadic/d-TGA, HLHS, VSD, ASD, mitral atresia, hypoplastic LV, subvalvar and valvar PS |
| 10 | F | unbalanced translocation | 370 k | arr 2q37.3(237239911-242692820)x3, arr 10q26.13q26.3(125436928-135320785)x1 |
5.5 Mb, 9.9 Mb | not analysed | not analysed | familial/dextrocardia with Rt. aortic arch, atrial inversion, CAVC, SVC abnls., abd. SI, asplenia |
| 11 | M | mosaic unbalanced translocation | 1 M, oligo | arr (2)x2 hmz mos, 7q22.1q36.3(98613389-158815293)x2-3, arr 10q22.1q26.3(73126274-135374311)x1-2 |
62.2 Mb, 60.2 Mb | not analysed | not analysed | sporadic/unbalanced AVC, single outlet RV, TAPVR; abd. SI, asplenia |
| 12 | M | mosaic gain | 1 M, oligo | arr 5q11.2q35.3(51392113-180837635)x2-3 | 129.4 Mb | arr 5q11.2q35.3(51750061-180857866)x2-3 | 129.1 Mb | sporadic/CHD |
| 13 | F | loss | 1 M | arr 1p34.3p34.1(36507566-45013872)x2-3 | 8.5 Mb | not analysed | not analysed | sporadic/d-TGA, VSD, ASD, DORV, mod. dil. RV/RA, mild RV hypertrophy, large tortuous PDA, excessive aortopulmonary collaterals, DD (MRI: 2 small sites of leukomalacia in white matter of frontal lobes) |
aFor the purposes of this and all subsequent tables, array-CGH is listed as oligo array, while SNP-arrays are designated as 370 or 1 M depending on number of included markers (370 000 versus 1 000 000).
bLinear positions according to Build 36, hg18. Standard cytogenetic nomenclature is used.