Table 2.
Clinical outcomes of constitutional chromothripsis.
| References | Chromosome regions involved in chromothripsis | Chromothripsis detection method | Imbalance (size, copy number alterations) | Affected genes | Phenotype of a carrier(s) |
|---|---|---|---|---|---|
| Bertelsen et al., 2016; Nazaryan-Petersen et al., 2016 | 3q22.3-q23 5q23.1 |
Conventional cytogenetics, mate-pair sequencing | Four deletions (2–110 kb) | Truncated genes: PPP2R3A, CLDN18, A4GNT, DBR1, HSD17B4, ATR Fusion genes: CLDN18-HSD17B4, HSD17B4-DBR1 Deleted genes: DZIP1L |
No apparent association with a disorder |
| Anderson et al., 2016 | 13q33.1-q33.3 Xp11.22-p21.3 Xq21.31-q22.1 |
Conventional cytogenetics, FISH, aCGH | 10 deletions (327 kb – 8 Mb): a total 4.4 Mb of chr. 13 material and 28.1 Mb of chr. X material | Deleted genes: Chr. 13 – ERCC5, SLC10A2 Chr. X – IL1RAPL1, DMD, GK, NROB1, CYBB, OTC, RPGR, TSPAN7, XK, ATP6AP2, BCOR, CASK, CFP, KDM6A, MAOA, NDP, NYX, RBM10, RP2, SYN1, UBA1, USP9X, ZNF81, BMP15, CACNA1F, CLCN5, FOXP3, HSD17B10, IQSEC2, KDM5C, PHF8, FGD1, HUWE1, HSD17B10, DIAPH2, SRPX2 |
Developmental delay and dysmorphism |
| Weckselblatt et al., 2015 | 1q21 4q31 7p14.3 15q22 |
Conventional cytogenetics, FISH, targeted sequencing | 530-kb deletion of chr. 1 material; 4,2-Mb duplication of chr. 7 material | No disrupted genes by the breakpoints | Developmental delay, autism, intellectual disability, and/or congenital anomalies |
| 3q25-q26 8q23 9p22-p24 11p14.1 3q21.1 |
Conventional cytogenetics, FISH, WGS | Mb-sized deletions of chr. 8 and 9 material; a total of 99 bp deleted of other chromosomes material | Disrupted genes by the breakpoints: PTPRD, SH3GL2 | Developmental delay, autism, intellectual disability, and/or congenital anomalies | |
| 2q32-qter 3q13 7q21.11-q22.1 10q21.3 11q14.1 |
Conventional cytogenetics, FISH, WGS | 800-kb deletion of chr. 7 material, 2.2-Mb deletion of chr. 11 material; in addition, there are 55 total bp deleted at breakpoint junctions on other chromosomes | Disrupted genes by the breakpoints: GRM3, KPNA1, DLG2, CACNA2D1, GULP1, COL5A2, KCNH7, PCLO, TRRAP | Developmental delay, autism, intellectual disability, and/or congenital anomalies | |
| Nazaryan et al., 2014 | 2p16.1-p22.1 5p14.2-p15.2 7p21.3-q31.1 |
Conventional cytogenetics, FISH, mate-pair sequencing | No copy number alterations | Truncated genes: CDH12, DGKB, FOXP2 | Global developmental and psychomotor delay, severe speech disorder |
| Gamba et al., 2015 | 1p36.33-p35.3 | Conventional cytogenetics, aCGH | Five deletions: 0.83, 0.94, 1.4, 1.7, 3.7 Mb 1 duplication: 5.9 Mb | No data | Multiple congenital malformations presenting some features overlapping the 1p36 deletion phenotype |
| Gu et al., 2013 | 5p13.3-p15.33 7p22 7q32 11q23 21q21 |
Conventional cytogenetics, FISH, aCGH | No copy number alterations | No data | Phenotypically normal |
| 5p13.3-p15.33 11q23 |
Conventional cytogenetics, FISH, aCGH | Three deletions: 2.89, 0.56, and 3.21 Mb | Deleted genes: LOC340094, ADAMTS16, KIAA0947, FLJ33360, MED10, UBE2QL1, LOC255167, NSUN2, SRD5A1, PAPD7, MIR4278 | Phenotypically normal | |
| 5p13.3-5p15.33 | Conventional cytogenetics, FISH, aCGH | ∼26.22-Mb deletion | No data | Developmental delay, dysmorphic and autistic features | |
| Kloosterman et al., 2011 | 1p32.3 4q24 10q21.1 |
Conventional cytogenetics, SNP array, mate-pair sequencing | Small deletions and duplications (<50 bp) | Disrupted gene: PCDH15 | Severe psychomotor retardation, speech delay, hypertelorism and kyphoscoliosis |
| Slamova et al., 2018 | 1q23-q25 6q15-q24 14q13? 18p11.2-p11.3 18q11.2 |
Conventional cytogenetics, FISH, aCGH, mate-pair sequencing | Two deletions: 0.7 and 2.5 Mb | Deleted genes: DNM3, PIGC, C1ORF105, SUCO, NMBR, VTA1, ADGRG6, HIVEP2, AIG1, ADAT2, PEX3, FUCA2, PHACTR2, LTV1, ZC2HC1B, PLAGL1, SF3B5, STX11, UTRN, PAX9 Disrupted genes by the breakpoints: FILIP1, PHIP, HMGN3, AK097143, GAREM |
Developmental and growth delay |
| Wang et al., 2015 | 19p13.13-p13.2 19p12 19q12 19q13.11-q13.12 |
Conventional cytogenetics, FISH, aCGH | Four duplications: 4.3, 0.98, 1.12, and 5.13 Mb | No data | Subtle dysmorphic features |
| Macera et al., 2015 | 3p24.3 5q14 7q35 9p23 18p11.31 18q21.31 |
Conventional cytogenetics, FISH, SNP array, NGS | No loss or gain of chromosomal material at any of the breakpoints | Disrupted genes by the breakpoints: CNTN6, TBC1D5, CNTNAP2, PTPRD, L3MBTL4, LOC1001304840, WDR7 | Bilateral ventriculomegaly (13 and 15 mm), colpocephaly, with partial agenesis of the corpus callosum, and an absent left kidney and small right kidney |
| Kurtas et al., 2018 | 22q13.1-q13.3 | Conventional cytogenetics, FISH, aCGH, WGS, WES | Two duplications: 2.4 Mb, 148 kb 1 deletion: 8.4 Mb | Disrupted genes by the breakpoints: EP300, NFAM1, MYO18B, GTPBP1 | Phelan-McDermid syndrome |
| Genesio et al., 2015 | 9p21-q31 | Conventional cytogenetics, FISH, aCGH | Two deletions: 176.56 kb, 7.44 Mb | Deleted genes: RORB, TRPM6, NMRK1, OSTF1, GNAQ, and the critical region of the 9q21.13 deletion syndrome | Platelet disorder and thyroid dysfunction in addition to the classical neurobehavioral phenotype of the 9q21.13 microdeletion syndrome |
| Del Rey et al., 2016 | 2q34-q37.3 | Conventional cytogenetics, FISH, HR-CGH, MLPA | Deletion: 2.58 Mb duplication of 2q34q37.2 | Deleted genes: K1F1A, PASK, HDLBP, FARP2 | Multiple congenital disorders and intellectual disability |
| Fontana et al., 2014 | 1q41 1q43 9p24.3 21q22.12 |
Conventional cytogenetics, aCGH | Four deletions: 5.23, 1.33, 0.15871, and 0.826 Mb | Deleted genes: SMYD2, PTPN14, CENPF, KCNK2, KCTD3, USH2A, ESRRG, SPATA17, RRP15, TGFB2, CHRM3, KANK1, RCAN1, CLIC6, RUNX1 | Loeys–Dietz syndrome, type 4; borderline mental impairment |
| Kurtas et al., 2019 | 3q22.3-q26.2 | Conventional cytogenetics, FISH, aCGH, paired-end sequencing | Deletion: 6.8 kb | Disrupted genes by the breakpoints: ROPN1B, NAALADL2, TF | Healthy |
| 3q22.3-q26.2 | Conventional cytogenetics, FISH, aCGH, paired-end sequencing | Duplication: 10 Mb deletion: 5 Mb | Disrupted genes by the breakpoints: ROPN1B, NAALADL2, TF | Multiple phenotypic abnormalities and psychomotor delay | |
| chr. 6 14q31.3 |
Conventional cytogenetics, FISH, aCGH, paired-end sequencing | Two deletions: 5.3 and 3.7 kb | Disrupted genes by the breakpoints: OPRM, RNGTT | Healthy | |
| chr. 6 14q31.3 |
Conventional cytogenetics, FISH, aCGH, paired-end sequencing | Deletion: 1 Mb | Disrupted genes by the breakpoints: OPRM, RNGTT | Healthy | |
| 15q15.1 6p21.3-p25.1 6q14.2 6q21-q22.31 7q32.3 |
Conventional cytogenetics, FISH, SNP-CGH array, paired-end sequencing | Deletion: 6 kb | Disrupted genes by the breakpoints: CASC5, RPF2, CHCHD3, CLVS2 | Healthy | |
| 15q15.1 6p21.3-p25.1 6q14.2 6q21-q22.31 7q32.3 |
Conventional cytogenetics, FISH, SNP-CGH array, paired-end sequencing | Four deletions up to 100 bp 6-bp microduplication | Disrupted genes by the breakpoints: CASC5, RPF2, CHCHD3, CLVS2. One parental breakpoint junction is absent | Developmental and speech delay, dysmorphic features |
aCGH, array comparative genomic hybridisation; FISH, fluorescent in situ hybridisation; HR-CGH, high resolution comparative genomic hybridisation; MLPA, multiplex ligation-dependent probe amplification; NGS, next generation sequencing; SNP array, single nucleotide polymorphism array; WGS, whole genome sequencing; WES, whole exome sequencing.