Cytoonearray-Clinical Diagnostic Tool
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Targeted chromosomal microarray for detecting abnormalities related to micro-deletions and micro-duplications Detects chromosomal abnormalities and familial diseases of fetuses and infants. High-density probe deployment, detecting chromosomal micro-deletions and micro-duplications. In addition to detecting aneuploidy diseases (such as Down's syndrome), CytoOneArray can simultane- ously detect 372 genetic abnormalities (331 diseases and 41 sub-telomeric regions). Emphasis on detecting developmental delays (DD) and intellectual disabilities (ID). Excludes common CNVs in non-specific areas. From analyzing data to the report output, CytoOneArray is easy to operate with our software! [ Array Spec. ] 2 0 Database UCSC hg19 -2 Probe length 57-63 mer only reports disease-related CNVs Disease regions 331 Subtelomeres 41 Disease region 10 - 30 Kb probe resolution 2 0 Total probes 33,255 -2 、 Sample type blood amniotic fluid DNA、tissue Other CMAs report benign CNVs, which may affect clinical interpretation. Missing pathogenic regions may also lead to medical disputes. Application Postnatal Testing • Identifies chromosomal abnormalities from blood DNA • Provides relevant phenotype information • Similar to performing 372 FISH experiments simultaneously Prenatal Testing • Identifies chromosomal abnormalities from amniotic fluid cell DNA • Provides relevant genotype information • Offers a much higher diagnostic yield Process Requisition form & Sample Array Report Informed consent Collection Analysis Explains test results 1 Comparisons with Other Methods FISH Chromosomal Method Karyotyping (Fluorescence in situ microarray Hybridization) Target ChromosomeChromosome fragment Chromosome fragment Resolution 5 - 10 Mb 10 Kb - 100 Kb 10 - 50 Kb To detect specified To detect micro- To detect chromosome Major micro-duplications, duplications and number and large micro-deletions and micro-deletions application physical abnormality structural changes across whole genome Unable to detect Need to know Unable to discriminate Limitation micro-duplications abnormal chromosome balanced chromosome and micro-deletions position prior to test structural changes David Miller et al. The American Journal of Human Genetics 86, 749–764 (2010) Chromosomal microarray analysis should be the first-line genetic test in pregnancies where ultrasound screens uncover signs of fetal abnormalities, according to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine. ACOG committee opinion, Number 581 (2013) 2 Perfect Support CytoOneArray provides an integrated service system, which starts from array design, to process control of detection, to report generation (Figure A). Figure B depicts an online disease database available to physicians after report generation. This chain of services was designed to assist the diagnosis. A. Software From analyzing data to generating a report, everything is simple and secure! [鍵入文字] 華聯染色體晶片檢測報告 報報告告編編號號 CY2013-00-000-v1 採採樣樣日日期期 2014-6-6 收收檢檢日日期期 2014-6-8 檢檢體體編編號號 CY2013-00-000 檢檢體體類類別別 羊水 送送檢檢原原因因 高齡產婦; 有家族遺傳病史 送送檢檢醫醫師師 ○○○醫師 報報告告日日期期 2014-06-20 諮諮詢詢專專線線 (03)578-1168 分機 506 cytoinfo@onearray.com 華聯生技股份有份公司 www.OneArray.com 0800-777-988 - 0 - cytoinfo@onearray.com CytoOA-tw-postnatal V1.0 B. Online disease database References for diagnosis Multiple search tools • by Key word • by Cytoband • by Disease name Link to OMIM database 300068 ANDROGEN INSENSITIVITY SYNDROME; AIS Alternative titles; symbols TESTICULAR FEMINIZATION SYNDROME; TFM ANDROGEN RECEPTOR DEFICIENCY Cytogenetic location: Xp12 Gene Phenotype Relationships Disease info & reference Chromosome 1p36 deletion syndrome 1p36 607872 Deletion of 1p36.13 to 1p36.33, major in 1p36.2 Growth retardation, pre- and postnatal, Eyes/Ears deafness, and abnormal in appearance. (Detail) GeneReviews: 1p36 deletion syndrome 3 Demo Report Abnormality result is reported: Chromosomal Microarray Result ISCN nomenclature arr 7q11.23 (72,726,605-74,096,842)x1 Dosage Variation 1.370 Mb-microdeletion at chromosome 7q11.23 was detected. No . 7 chr. Abnormal chromosome Analysis Result Interpretation: 1.370 Mb-microdeletion at chromosome 7q11.23 was detected. According to the clinical literature, Williams- Beuren syndrome (WBS) is a contiguous gene deletion syndrome resulting from the deletion on chromosome 7q11.23. Chromosome Ideogram: Copy-number variations (CNVs) are displayed on the corre- sponding locations in the genome. Red regions indicate copy-number losses, and blue regions indicate copy-number gains. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y 4 Disease Name Cytoband OMIM Disease Name A ACMG Autism possible region 2q37.1 – Chromosome 2q24.3 deletion ACMG Autism possible region 13q14.2 – Chromosome 3pter-p25 deletion syndrome ACMG Autism possible region 18q21.1 – Chromosome 3q29 microdeletion syndrome Adrenal hypoplasia, congenital (AHC) Xp21.2 300200 Chromosome 4p16.1 duplication Adrenoleukodystrophy (ALD) Xq28 300100 Chromosome 4q21 deletion syndrome Agammaglobulinemia, X-linked 1 (XLA) Xq22.1 300755 Chromosome 6p22 deletion Alagille syndrome 1 (ALGS1 ) 20p12.2 118450 Chromosome 6pter-p24 deletion syndrome Albinism, oculocutaneous, type II (OCA2) 15q12-q13.1 203200 Chromosome 7q31.2 microdeletion/microduplication Alpha thalassemia/mental retardation syndrome 16p13.3 141750 Chromosome 8p22-p23.1 duplication Alport syndrome, X-linked (ATS) Xq22.3 301050 Chromosome 8q11 duplication Alzheimer disease 1, familial (AD1) 21q21.3 104300 Chromosome 8q21 microdeletion ~ A Androgen insensitivity syndrome (AIS) Xq12 300068 Chromosome 9p deletion syndrome Angelman syndrome (AS ) 15q11.2-q13.1 105830 Chromosome Xp11.3 deletion syndrome Aniridia (AN) 11p13 106210 Chromosome Xp22 deletion syndrome K Asperger syndrome,X-linked, susceptibility to, 1 (ASPGX1) Xq13.1 300494 Chronic granulomatous disease, X-linked (CGD) Autism (contain A2BP1 gene) 16p13.3 – Cleft palate, isolated (CPI) Autism (contain ANKRD11 gene) 16q24.3 – Cleidocranial dysplasia (CCD) Autism (contain CDH8 gene) 16q21 – Coffin-Lowry syndrome (CLS) Autism (contain CNTNAP1 gene) 17q21.2-q21.31 – Cornelia de Lange syndrome 1 (CDLS1) Autism (contain DLGAP2 gene) 8p23.3 – Cornelia de Lange syndrome 2 (CDLS2) Autism (contain DPP10 gene) 2q14.1 – Cortical dysplasia-focal epilepsy syndrome Autism (contain DPP6 gene) 7q36.2 – Cowden syndrome 1 (CWS1) Autism (contain NLGN1 gene) 3q26.31 – Craniofacial dysostosis with short stature Autism (contain PCDH9 gene) 13q21.32 – Craniofrontonasal syndrome (CFNS) Autism susceptibility 15 (AUTS15) 7q35-q36.1 612100 Craniosynostosis, type 2 (CRS2) Autism susceptibility 16 (AUTS16) 3q24 613410 Cri-du-Chat syndrome Autism susceptibility 17 (AUTS17) 11q13.3-q13.4 613436 Currarino syndrome Autism susceptibility 6 (AUTS6) 17q11.2 609378 Cystinosis, Nephropathic (CTNS) Autism susceptibility, X-linked 2 (AUTSX2) Xp22.32-p22.31 300495 D Dandy-Walker syndrome (DWS) Autism, susceptibility to, X-linked 3 (AUTSX3) Xq28 300496 Danon disease Axenfeld-Rieger syndrome, type 1 (RIEG1) 4q25 180500 Deafness, autosomal dominant 10 (DFNA10) Axenfeld-Rieger syndrome, type 3 (RIEG3) 6p25.3 602482 Diaphragmatic hernia 2 (DIH2) B Bannayan-Riley-Ruvalcaba syndrome (BRRS) 10q23.2-q23.31 153480 Diaphragmatic hernia 3 (DIH3) Bartter syndrome, antenatal, type 2 11q24.3 241200 Diaphragmatic hernia, congenital Basal cell nevus syndrome (BCNS) 9q22.32 109400 DiGeorge syndrome (DGS) Beckwith-Wiedemann syndrome (BWS) 11p15.5-p15.4 130650 DiGeorge syndrome/velocardiofacial syndrome complex-2 Blepharophimosis, ptosis, and epicanthus inversus (BPES) 3q22.3-q23 110100 DiGeorge syndrome/velocardiofacial syndrome complex-2 Borjeson-Forssman-Lehmann syndrome (BFLS) Xq26.2 301900 Dihydropyrimidine dehydrogenase deficiency Brachydactyly, type C (BDC) 20q11.22 113100 Down syndrome Brachydacytly-mental retardation syndrome (BDMR) 2q37.3 600430 Duane-radial ray syndrome (DRRS) Branchiootorenal syndrome 1 (BOR1) 8q13.2-q13.3 113650 Dyggve-Melchior-Clausen disease (DMC) Buschke-Ollendorff syndrome (BOS) 12q14.2-q14.3 166700 E Epilepsy, childhood absence, susceptibility to, 5 (ECA5) C Campomelic dysplasia (CMPD) 17q24.3 114290 Epilepsy, X-linked, with variable learning disabilities and Cardiomyopathy, dilated, 1J (CMD1J) 6q23.2 605362 behavior disorders Cat eye syndrome (CES) 22q11.1-q11.21 115470 Epileptic encephalopathy, early infantile, 1 (EIEE1) Cerebral creatine deficiency syndrome 1(CCDS1) Xq28 300352 Epileptic encephalopathy, early infantile, 1 (EIEE1) Charcot-Marie-Tooth disease type 1A (CMT1A ) 17p12 118220 Epileptic encephalopathy, early infantile, 3 (EIEE3) CHARGE syndrome 8q12.1-q12.2 214800 Epileptic encephalopathy, early infantile, 4 (EIEE4) Chondrodysplasia punctata 1, X-linked recessive (CDPX1) Xp22.33 302950 Epileptic encephalopathy, early infantile, 6 (EIEE6) Chondrodysplasia, Grebe type 20q11.22 200700 Epileptic encephalopathy, early infantile, 8 (EIEE8) Choroideremia (CHM) Xq21.2 303100 Epileptic encephalopathy, early infantile, 9 (EIEE9) Chromosome 10q23 deletion syndrome 10q23.1-q23.31 612242 F Fabry disease Chromosome 10q26 deletion syndrome 10q26.3 609625 Familial adenomatous polyposis 1 (FAP1) Chromosome 12p13 microdeletion 12p13.31 – Feingold syndrome 1 (FGLDS1) Chromosome 12q24.21-q24.23 microduplication 12q24.21-q24.23 – Focal dermal hypoplasia (FDH) Chromosome 13q12 microduplication 13q12.11 – Forebrain defects Chromosome 13q33q34 microdeletion 13q33.3-q34 – Fragile X mental retardation syndrome Chromosome 14q11-q22 deletion syndrome 14q11.2 613457 G Glycerol kinase deficiency