Table 2 Genomic imbalance and uniparental disomy detected by 500K GeneChip® AGH in the new cohort.
Patient | Change | Location | SNP Count | Start → End | Size (bp) | Validation | Phenotype | RefSeq Genes Involved* | Comments | Interpretation |
|---|---|---|---|---|---|---|---|---|---|---|
9133 | Deletion | 1p36.32-p36.33 | 198 | 769,185 → 3,581,308 | 2,812,123 | FISH, MLPA | 9 year-old female with obesity, moderate cognitive impairment, myoclonus, polyphagia, hypotonia, narrow frontal area, deep-set eyes, prominent orbital rims, short nose with low nasal bridge and upturned nasal tip, midface retrusion, short philtrum, tented upper lip, thoracic kyphosis, small distal phalanges of the toes, strabismus, and 11 ribs | ~70 genes including AGRN, GNB1, PEX10, PRKCZ, SKI, and TP73 | This CNV is included in the 1p36 deletion syndrome critical region, and the patient's clinical features are compatible with that syndrome [73]. | Pathogenic |
873 | Duplication†| 2q37 | 1801 | 231,577,285 → 242,663,303 | 11,086,018 | FISH, MLPA | 15 year-old male with severe cognitive impairment, birth weight < 1st centile, birth length < 1st centile, head circumference at birth < < 10th centile, hypotonia, microcephaly, contractures of hips and knees, hypoplastic scrotum, undescended testes, prominent, cup-shaped ears, narrow bifrontal diameter, broad nasal root, prominent epicanthal folds, bilateral clinodactyly V, ataxic gait, progressive joint contractures and muscle wasting of lower extremities, mixed hearing loss and hypoplastic inferior cerebellar vermis, partial dysgenesis of corpus callosum, and narrow pons and brain stem on MRI | ~100 genes including AGXT, ATG16L1, CAPN10, CHRND, CHRNG, COL6A3, D2HGDH, GBX2, HDAC4, MLPH, PDCD1, PER2, SAG and UGT1A1 |  | Pathogenic |
|  | Deletion†| 10q26.13 | 1920 | 126,415,527 → 134,032,911 | 7,617,384 |  |  | ~75 genes including ADAM12, CTBP2, DOCK1, DPYSL4, FGFR2, OAT, and UROS |  |  |
6473 | Deletion | 4p16.3 | 337 | 190,631 → 3,277,436 | 3,086,805 | Cytogenetic re-analysis, FISH | 3 year-old male with fetal growth retardation, length 2 standard deviations below the mean for age, weight 3-4 standard deviations below the mean, head circumference 3-4 standard deviations below the mean, global developmental delay, seizures, triangular face, small jaw, posteriorly rotated ears, 2° hypospadias, and ataxia | ~45 genes including ADD1, FGFR3, HTT, IDUA, LETM1, PDE6B, SH3BP2, and WHSC1 | The deletion in this patient includes the Wolf- Hirschhorn syndrome critical region, and the clinical features are compatible with that syndrome [74]. | Pathogenic |
5814 | Deletion†| 4p16.1-p16.3 | 1520 | 13,255 → 8,472,657 | 8,459,402 | Cytogenetic re-analysis, MLPA | 13 month-old female with length below the 3rd centile, microcephaly, developmental delay, bilateral preauricular pits, and submucus cleft palate | ~90 genes including ADD1, ADRA2C, CRMP1, EVC | The deletion includes the Wolf- Hirschorn syndrome critical region. | Pathogenic |
|  | Duplication†| 8p23.1-p23.3 | 2579 | 180,568 → 6,898,076 | 6,717,508 |  |  | 20 genes including ARHGEF10, CLN8, DLGAP2, and MCPH1 |  |  |
216 | Deletion | 6p21.33 | 42 | 29,937,087 → 30,026,517 | 89,430 | MLPA | 18 year-old male with postnatal onset growth retardation, unilateral sensorineural deafness, narrow face, bulbous nasal tip and mild intellectual disability. | HCG9, MICD and 5 pseudogenes | Deletion is homozygous in child, heterozygous in both parents (not de novo mutation) | Not pathogenic for ID |
3160 | Deletion | 6 q21-q22.31 | 1596 | 111,979,175 → 121,506,916 | 9,527,741 | FISH | 8 year-old female with moderate developmental delay, hypotonia, microcephaly, brachycephaly, epicanthic folds, small ears with hypoplastic lobes, and micrognathia | ~40 genes including ASF1A, COL10A1, FRK, FYN, GOPC, HDAC2, LAMA4, MCM9, PLN, TSPYL1, and WISP3 |  | Pathogenic |
2200 | Deletion | 7p15.3 | 2320 | 14,141,506 → 24,950,414 | 10,808,908 | FISH | 11 1/2 year-old female with head circumference at the 2nd centile, mild cognitive impairment, sensorineural hearing loss, cleft palate, craniosynostosis, unilateral ptosis and esotropia, orbital rim hypoplasia, malar and midface hypoplasia, low-set ears with incomplete out-folding of superior helix, brachydactyly and syndactyly of digits, broad thumbs, decreased range of motion in elbows, and leg length discrepancy | ~40 genes including DFNA5, DGKB, DNAH11, FAM126A, HDAC9, IL6, and RAPGEF5 |  | Pathogenic |
9938 | Deletion | 7q22.1 | 170 | 98,211,585 → 100,553,755 | 2,342,170 | FISH | 14 year-old female with height < 5th centile, weight < 5th centile, head circumference < 5th centile, severe cognitive impairment, left sensorineural hearing loss, close-set eyes, broad nasal root, marked retrognathia, high-arched palate, small and narrow feet, short 2-5th toes with hypoplastic nails, atrio-vetricular septal defect, and polyarticular arthritis | ~70 genes including ACHE, ACTL6B, CYP3A5, EPO, MUC3A, SERPINE1, SMURF1, and TFR2 |  | Pathogenic |
1594 | Duplication | 8 q12 | 1220 | 58,388,614 → 65,306,097 | 6,917,483 | FISH | 1 1/2 year-old female with height > 97th centile, head circumference at 2nd-5th centile, developmental delay, Duane anomaly, broad glabella, epicanthic folds with telecanthus, upslanting palpebral fissures, pre-auricular pits, large ears, atrial and ventricular septal defects, and renal reflux | 15 genes including ASPH, CHD7, RAB2A, RLBP1L1, TOX, and TTPA |  | Pathogenic |
663 | Deletion | 9 p13.3 | 800 | 34,144,847 → 38,736,451 | 4,591,604 | FISH | 5 1/2 year-old female with height at the 5th centile, developmental delay, tremor, ocular hypertelorism, epicathal folds, double hair whorl, bilateral ptosis, short upturned nose, flattened philtrum, underdeveloped genitalia, and pigmentary retinal changes | ~75 genes including CNTFR, DNAI1, DNAJB5, FANCG, GALT, GBA2, GNE, GRHPR, NPR2, PAX5, RECK, SHB, TPM2, UNC13B, and VCP | The deleted region in this patient is completely included in the region deleted in patient 9346. | Pathogenic |
9346 | Deletion | 9p11.2-p13.3 | 880 | 33,702,471 → 44,744,675 | 11,042,204 | FISH | 9 1/2 year-old female with moderate cognitive impairment, seizures, tremor, cataract, broad frontal area with bossing, arched eyebrows, low nasal bridge, and short, upturned nose | ~85 genes including CNTFR, DNAI1, DNAJB5, FANCG, GALT, GBA2, GNE, GRHPR, NPR2, PAX5, RECK, SHB, TPM2, UNC13B, and VCP | The deleted region in this patient includes the entire segment deleted in Patient 663. | Pathogenic |
523 | Deletion | 9q34.3 | 36 | 139,516,033 → 139,814,485 | 298,452 | FISH | 4 year-old female with moderate developmental delay, hypotonia, microcephaly, flat face with upslanting palpebral fissures, ocular hypotelorism, synophrys, and anteverted nares | 7 genes including EHMT1 | This deletion is within the critical region for the 9q subtelomeric deletion syndrome[75], and the child's clinical features are compatible with that syndrome. | Pathogenic |
8056 | Mosaic Trisomy | 9 | 27,641 | whole chromosome | FISH | 2 1/2 year-old male with weight < 5th centile, developmental delay, preauricular skin tags, hypospadias, and cryptorchidism | Numerous | Clinical features compatible with mosaic trisomy 9 syndrome[76, 77] | Pathogenic | |
6904 | Uniparental Disomy | 11p11.2-pter | See Table 3 | 196,767 → 44,589,530 | 44,392,763 | Micro-satellite markers | 11 year-old female with height < 5th centile, gross and fine motor delay, hypotonia, and moderate mental handicap | Numerous | Mosaic paternal isodisomy; phenotype not compatible with Beckwith-Wiedemann syndrome | Uncertain |
9897 | Deletion | 13q33.3-q34 | 530 | 107,271,189 → 109,368,996 | 2,097,807 | FISH | 10 year-old female with fetal growth retardation, moderate cognitive impairment, upslanting palpebral fissures, and retrognathia | 6 genes including IRS2, LIG4, and MYO16 |  | Pathogenic |
818 | Deletion | 14q11.2 | 24 | 21,929,710 → >22,036,502 | 106,792 | Fosmid FISH (variable)§ | 6 1/2 year-old male with weight < 5th centile, height at 5th centile, mild cognitive impairment with particular delay in language, mild mid-face hypoplasia with narrow high-arched palate, mild micrognathia, pre-auricular pit, joint laxity, bilateral clinodactyly of hands, and bilateral 2-3 syndactyly of toes | Multiple T-cell receptor alpha-chain V, J, and region genes | Highly polymorphic region | Not pathogenic for ID |
1658 | Uniparental Disomy | 16 | See Table 3 | Whole chromosome | Whole chromosome | Micro-satellite markers | 5 year-old female with normal growth, severe mental handicap, seizures, self-abusive behaviour, deep and dark creases under the eyes, mild mid-face hypoplasia, and large mouth | Numerous | Â | Uncertain |
2106 | Deletion | 17q21.31 | 149 | 41,049,321 → 41,564,451 | 515,130 | FISH | 15 year-old male with fetal growth retardation, mild cognitive impairment, attention deficit disorder, sagittal craniosynostosis, long face with malar hypoplasia and mild rectrognathia, short and upslanting palpebral fissures, low-set ears, unilateral cryptorchidism, partial agenesis of the corpus callosum, and dilatation of the aortic root | 5 genes including MAPT | The deleted segment includes the critical region for the 17q21.31 deletion syndrome, [78] and this patient's clinical features are compatible with that syndrome. | Pathogenic |
8619 | Deletion | 21q22.11 | 13 | 33,902,218 → 34,087,893 | 185,675 | Agilent 244 K AGH | 24 year-old male with prenatal and postnatal growth retardation, moderate to severe intellectual disability, severe hypotonia, microcephaly, metopic craniosynostosis, cleft palate, down-slanting palpebral fissures, low-set ears, wide nasal base, retrognathia, tetralogy of Fallot, cryptorchidism, and joint hyperextensibility | 5 genes including SYNJ1 | No polymorphisms of region reported | Uncertain |
|  | Deletion | 22q11.2 | 110 | 19,062,809 → 19,785,125 | 722,316 | FISH |  | 14 genes including BCR, DGCR8, HIRA, MAPK1, PRODH, SNAP29, SEPT5, SERPIND1, and TBX1 | The deleted segment is included in the 22q11 deletion syndrome critical region, and the phenotype is compatible with other reported cases of distal 22q11.2 microdeletion [79–81] | Pathogenic |
9979 | Duplication | 22q11.21 | 57 | 19,429,297 → 19,791,607 | 362,310 | FISH | 20 year-old female with short stature, mild mental deficiency, cleft palate, and micrognathia | 9 genes including PI4KA SERPIND1, LZTR1, SNAP29 | Polymorphic region | Uncertain |
1128 | Duplication | Xq12-q21.1 | 475 | 67,088,023 → 76,204,344 | 9,116,321 | FISH | 11 year-old male with normal growth, severe developmental delay, hypotonia, brachycephaly, bilateral epicanthic folds, and posteriorly rotated ears with hypoplastic helices | ~60 genes including ABCB7, DLG3, EDA, EFNB1, GJB1, IGBP1, IL2RG, OPHN1 NAP1L2, NLGN3, PHKA1, SLC16A2, TAF1, and ZDHHC15 |  | Pathogenic |