https://orcid.org/0000-0002-7800-8665
Figures & data
Table 1. Overview of the different techniques used to detect copy number variants.
There are four different categories in this figure: reader, eraser, writer and remodeler proteins. On the outside of the figure there are open circles that denote recessive inheritance and closed circles that denote dominant inheritance. In addition, the disorder phenotypes are shown in different colors, dysmorphic features (green), growth retardation (blue) and intellectual disability (orange).
This figure is adapted with permission from [Citation7], © Bjornsson.
![Figure 1. Current episignatures detectable by EpiSign™ V3. There are four different categories in this figure: reader, eraser, writer and remodeler proteins. On the outside of the figure there are open circles that denote recessive inheritance and closed circles that denote dominant inheritance. In addition, the disorder phenotypes are shown in different colors, dysmorphic features (green), growth retardation (blue) and intellectual disability (orange).This figure is adapted with permission from [Citation7], © Bjornsson.](/cms/asset/d1522f5f-6968-4023-a13e-ba916b077533/iepi_a_12324386_f0001.jpg)
(A) Deletions of the 22q11.2 region: those in red all share a common episignature including the two most proximal deletions. The four deletions represented by the blue horizontal bars do not share the common episignature. (B) Heatmap confirms that 22q11.2 deletion subjects (orange) can be differentiated from age and sex matched controls (blue) using selected CpG probes identified as the episignature. (C) Multidimensional scaling plot confirming the clustering of affected subjects from controls. (D) Support vector machine classifier model. This model was trained using the selected probes for the 22q11.2 episignature, 75% of controls and 75% of other neurodevelopmental disorders samples (blue). The remaining 25% of controls and other disorder samples were used for testing (grey). Plot demonstrates the specificity of the 22q11.2 episignature in differentiating affected cases from other neurodevelopmental disorders with mapped episignatures on the EpiSign™ clinical classifier.
22q11.2DS: 22q11.2 deletion syndrome; ADCADN: Cerebellar ataxia deafness and narcolepsy syndrome; AUTS18: Susceptibility to autism 18; BEFAHRS: Beck-Fahrner syndrome: BFLS: Borjeson–Forssman–Lehmann syndrome; BISS: Blepharophimosis intellectual disability SMARCA2 syndrome; CdLS: Cornelia de Lange syndrome; CHARGE: CHARGE syndrome; Chr16p11.2del: Chromosome 16p11.2 deletion syndrome; CSS: Coffi–Siris syndrome; CSS4: Coffin-Siris syndrome 4; CSS9: Coffin–Siris syndrome 9; Down: Down syndrome; Dup7: 7q11.23 duplication syndrome; DYT28: Dystonia 28; EEOC: Epileptic encephalopathy-childhood onset; FLHS: Floating Harbour syndrome; GTPTS: Genitopatellar syndrome; HMA: Hunter McAlpine craniosynostosis syndrome; HVDAS: Helsmoortel–van der Aa syndrome; ICF: Immunodeficiency-centromeric instability-facial anomalies syndrome; IDDSELD: Intellectual developmental disorder with seizures and language delay; Kabuki: Kabuki syndrome; KDVS: Koolen-De Vries syndrome; Kleefstra: Kleefstra syndrome; LLS: Luscan-Lumish syndrome; MKHK: Menke-Hennekam syndrome; MLASA2: Myopathy lactic acidosis and sideroblastic anemia 2; MRD23: Intellectual developmental disorder 23; MRD51: Intellectual developmental disorder 51; MRX93: Intellectual developmental disorder X-linked 93; MRX97: Intellectual developmental disorder X-linked 97; MRXSA: Intellectual developmental disorder X-linked syndromic Armfield type; MRXSCH: Intellectual developmental disorder X-linked syndromic Christianson type; MRXSCJ: Intellectual developmental disorder X-linked syndromic Claes-Jensen type; MRXSN: Intellectual developmental disorder X-linked syndromic Nascimento type; MRXSSR: Intellectual developmental disorder X-linked syndromic Snyder–Robinson type; PHMDS: Phelan–McDermid syndrome; PRC2: PRC2 complex (Weaver and Cohen-Gibson) syndrome; RENS1: Renpenning syndrome; RMNS: Rahman syndrome; RSTS: Rubinstein–Taybi syndrome; SBBYSS: Ohdo syndrome; Sotos: Sotos syndrome; TBRS: Tatton–Brown–Rahman syndrome; WDSTS: Wiedemann–Steiner syndrome; WHS: Wolf-Hirschhorn syndrome; Williams: Williams syndrome.
This figure is adapted with permission from [Citation74].
![Figure 2. 22q11.2 deletion syndrome demonstrating that episignatures can be mapped in copy number variant disorders and utilized in clinical testing. (A) Deletions of the 22q11.2 region: those in red all share a common episignature including the two most proximal deletions. The four deletions represented by the blue horizontal bars do not share the common episignature. (B) Heatmap confirms that 22q11.2 deletion subjects (orange) can be differentiated from age and sex matched controls (blue) using selected CpG probes identified as the episignature. (C) Multidimensional scaling plot confirming the clustering of affected subjects from controls. (D) Support vector machine classifier model. This model was trained using the selected probes for the 22q11.2 episignature, 75% of controls and 75% of other neurodevelopmental disorders samples (blue). The remaining 25% of controls and other disorder samples were used for testing (grey). Plot demonstrates the specificity of the 22q11.2 episignature in differentiating affected cases from other neurodevelopmental disorders with mapped episignatures on the EpiSign™ clinical classifier.22q11.2DS: 22q11.2 deletion syndrome; ADCADN: Cerebellar ataxia deafness and narcolepsy syndrome; AUTS18: Susceptibility to autism 18; BEFAHRS: Beck-Fahrner syndrome: BFLS: Borjeson–Forssman–Lehmann syndrome; BISS: Blepharophimosis intellectual disability SMARCA2 syndrome; CdLS: Cornelia de Lange syndrome; CHARGE: CHARGE syndrome; Chr16p11.2del: Chromosome 16p11.2 deletion syndrome; CSS: Coffi–Siris syndrome; CSS4: Coffin-Siris syndrome 4; CSS9: Coffin–Siris syndrome 9; Down: Down syndrome; Dup7: 7q11.23 duplication syndrome; DYT28: Dystonia 28; EEOC: Epileptic encephalopathy-childhood onset; FLHS: Floating Harbour syndrome; GTPTS: Genitopatellar syndrome; HMA: Hunter McAlpine craniosynostosis syndrome; HVDAS: Helsmoortel–van der Aa syndrome; ICF: Immunodeficiency-centromeric instability-facial anomalies syndrome; IDDSELD: Intellectual developmental disorder with seizures and language delay; Kabuki: Kabuki syndrome; KDVS: Koolen-De Vries syndrome; Kleefstra: Kleefstra syndrome; LLS: Luscan-Lumish syndrome; MKHK: Menke-Hennekam syndrome; MLASA2: Myopathy lactic acidosis and sideroblastic anemia 2; MRD23: Intellectual developmental disorder 23; MRD51: Intellectual developmental disorder 51; MRX93: Intellectual developmental disorder X-linked 93; MRX97: Intellectual developmental disorder X-linked 97; MRXSA: Intellectual developmental disorder X-linked syndromic Armfield type; MRXSCH: Intellectual developmental disorder X-linked syndromic Christianson type; MRXSCJ: Intellectual developmental disorder X-linked syndromic Claes-Jensen type; MRXSN: Intellectual developmental disorder X-linked syndromic Nascimento type; MRXSSR: Intellectual developmental disorder X-linked syndromic Snyder–Robinson type; PHMDS: Phelan–McDermid syndrome; PRC2: PRC2 complex (Weaver and Cohen-Gibson) syndrome; RENS1: Renpenning syndrome; RMNS: Rahman syndrome; RSTS: Rubinstein–Taybi syndrome; SBBYSS: Ohdo syndrome; Sotos: Sotos syndrome; TBRS: Tatton–Brown–Rahman syndrome; WDSTS: Wiedemann–Steiner syndrome; WHS: Wolf-Hirschhorn syndrome; Williams: Williams syndrome.This figure is adapted with permission from [Citation74].](/cms/asset/8be6d997-3d9d-4e97-8f96-d9793b4dc690/iepi_a_12324386_f0002.jpg)