Table 1. De novo CNVs in this cohort.
Sample | Cytoband | CNV | (Candidate) genes | Phenotypes | Validation procedure | Classification |
---|---|---|---|---|---|---|
DE21OSOUKBD100141 | 2q21.1 | hg19 chr2:g.(131349899_131486169)_(131991166_132057166)dup | Multiple incl. POTEJ, GPR148, AMER3, ARHGEF4, FAM168B, PLEKHB2 | OA/TOF | qPCR | Uncertain – likely benign |
DE12OSOUKBD100206 | 3p26.1 | hg19 chr3:g.(8519329_8521841)_(8551649_8554052)dup | LMCD1, LMCD1-AS1 | OA/TOF, tracheomalacia | qPCR | Uncertain |
SKZ_2111 | 7q35q36.3 | hg19 chr7:g.(143820444_143839360)_(159119486_159138663)del | Multiple incl. SHH, MNX1, SLC4A2 | TOF, abnormally placed anus, hypospadias, ventricle septal defects | FISH | Pathogenic |
SKZ_1810 SKZ_1810 | 8p22 11p14.3 | hg19 chr8:g.(17613606_17625479)_(17613606 _17844353)dup hg19 chr11:g.(21600567_21853276)_(22015682_22016670)del | FGL1, LFIRE1, MTUS1, PCM1 - | OA/TOF, aplastic left lung, anencephaly, craniorachyschisis, kyphosis, ventricular septal defect, pulmonary stenosis, radial club hand, hypoplastic thumbs, horseshoe kidney, broad thorax OA/TOF, aplastic left lung, anencephaly, craniorachyschisis, kyphosis, ventricular septal defect, pulmonary stenosis, radial club hand, hypoplastic thumbs, horseshoe kidney, broad thorax | MAQ assay MAQ assay | Uncertain – likely benign Uncertain – likely benign |
SKZ_1662 | 13q12.11 | hg19 chr13:g.(22685293_22688792)_(22978753_22981935)del | AK054845, LINC00540 | OA/TOF, tracheal stenosis, abnormal sacrum and kidney abnormality | MAQ assay | Uncertain |
SKZ_2111 | 16p13.11 | hg19 chr16:g.(14985615_15156180)_(16289532_17000304)dup | Multiple | TOF, abnormally placed anus, hypospadias, ventricle septal defects | MAQ assay | Uncertain – likely pathogenic |
SKZ_1307 | 21q22.2 | hg19 chr21:g.(40099972_40100880)_(40152372_40154748)dup | LINC00114 | OA/TOF, anal stenosis and long toes and fingers | MAQ assay | Uncertain – likely benign |
None of the parents had oesophageal atresia or trachea–oesophageal fistula. Therefore, main focus was on de novo CNVs. Depicted are the eight confirmed (with either qPCR or MAQ assay) de novo CNV out of 74 evaluated rare CNVs from the Erasmus MC – Sophia, Baylor College of Medicine and University of Bonn cohorts. qPCR/FISH/MAQ assay validation results are in Supplementary Figure 1. Chromosome region according to build hg19.