Case | Age | Clinical indication | CFM | Chromosomal abnormality (CytoRegion) | Size (Mb) | Bdev | Predicted mosaicism (%) | Karyotype before array | Confirmation | G-band result | FISH result | % mosaicism (single cell analysis)* |
1 | 3 y | Autism | No | Mosaic terminal duplication (2q31.1q37.3) | 66 | 0.046 | 17, 20, 9 | No | FISH (blood) | Normal (blood)† | nuc ish 2q31.1q37.3 (D2S447)x2 [82] /(D2S447)x3 [18] | 18% (FISH) |
2 | 5 y | DD | No | Mosaic interstitial duplication (3p14.3p21.1) | 2.9 | 0.060 | 21, 27, 12 | No | FISH (blood) | Normal (blood)† | nuc ish 3p14.3-p21.1 (RP11-875H7)x2 [79] /(RP11-875H7)x3 [21] | 21% (FISH) |
3 | 6 y | DD | Yes | Mosaic terminal duplication (5q32-qter) | 34 | 0.075 | 26, 35, 15 | Yes (N) | FISH (blood) | Normal (blood and skin†) | nuc ish 5q35(NSD1)x2 [79]/x3 [19] (blood) | 20% (FISH) |
4 | 2 m | Pre- and postnatal short stature, pulmonary stenosis, dysmorphism, mild DD | No | Unknown (chr 9) | 140 | 0.097 | 33, 48, 19 | Yes (N) | Not confirmed | Normal (blood)† | NP | – |
5 | FDIU | Encephalocoele, neuronal migration disorder | No | Unknown (13q12.3-qter) | 86 | 0.044 | 16, 19, 9 | Yes (N) | Not confirmed | Normal (amniotic fluid)† | NP | – |
6 | 21 m | DD, hypotonia, dysmorphism | No | Isodicentric (chr 18) | 76 | 0.022 | 8, 9, 4 | No | G-band | 46,XX,idic(18)(q21.1) [7]/46,XX[93] (blood) | NP | 7% (G-band) |
7 | 4 m | Hydrops, renal impairment, talipes | No | Small marker chr (18q11.1q11.2) | 3.4 | 0.074 | 26, 35, 15 | No | FISH/G-band | 47,XX,+mar(26)/48,XX,+marx2(2)/49,XX,+marx3(1)/46,XX(32) (blood); skin culture normal | nuc ish 18cen(D18Z1)x2 [23]/ x3 [27] (blood) |
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8 | 11 m | DD, short stature | No | Small marker chr (19p13.2). Ectopic centromere‡ | ∼1 | 0.091 | 31, 45, 18 | No | FISH | NP | ish der(19)(p13.32)(RP11-19I2+) (blood) | 30% (FISH) |
9 | 17 d | Hypoplastic aortic arch, microphthalmia, IUGR | No | Mosaic trisomy (chr 9)‡ | 140 | 0.086 | 30, 42, 17 | Yes (N) | FISH/G-band | 2/45 t9 (blood) (post-array review) | nuc ish 9cen(CEP9)x2 [77]/ x3 [23] (blood) | 23% (FISH) |
Mosaic UPD (chr 16) | 89 | 0.18 | 53, 113, 36 | Yes (N) | Microsatellite-PCR | chr 16 normal (blood) | Normal (blood smear)† | – | ||||
10 | 4 m | Hemihypertrophy | Yes | Mosaic segmental UPD (11p15.1-pter) | 20 | 0.10 | 33, 50, 20 | Yes (N) | Methylation studies | Normal (blood)† | NP | – |
11 | 2 m | Neonatal liver impairment, heart murmur, was non-dysmorphic and normal development and growth | – | Mosaic segmental UPD (16p11.2-pter)§ | 32 | 0.16 | 49, 94, 32 | No | By exclusion§ | Normal (blood)† | Normal (blood)† | – |
12 | 4 y | Macrocephaly, DD, soft tissue lesion in neck, frontal hair whorl | No | Mosaic segmental UPD (22q11.21-qter)§ | 32 | 0.10 | 33, 50, 20 | No | By exclusion§ | Normal (blood)† | Normal (blood)† | – |
Predicted mosaicism levels (%) were calculated from the deviation in BAF for heterozygous genotypes from the ‘typical’ state of 0.5. As there was no deviation in the LogR data to infer the chromosomal abnormality, the predicted level (%) of mosaicism for each case is provided for deletion, duplication and LCSH (bolded values indicate the likely abnormality based on follow-up studies).
↵* The per cent mosaicism as revealed by single cell analysis (ie, FISH or G-band chromosome analysis).
↵† 100 cells were analysed for these cases.
↵‡ Molecular analysis of parental samples for cases 8 and 9 showed no evidence of an abnormality involving these chromosomes.
↵§ Cases 11 and 12 were consistent with a segmental uniparental disomy based on normal cytogenetics obtained on cultured and uncultured peripheral blood.
BAF, B-allele frequency; BMI, body mass index; CFM, clinical features of mosaicism; DD, developmental delay; FDIU, fetal death in utero; FISH, fluorescence in situ hybridisation; IUGR, intrauterine growth retardation; LCSH, long continuous stretches of homozygosity; (N), normal karyotype result; NP, not performed; UPD, uniparental disomy.