Anemia Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: HE0401

The Blueprint Genetics Anemia Panel is a 68 gene test for genetic diagnostics of patients with clinical suspicion of hereditary anemia.

This panel is specifically designed for differential diagnosis of inherited anemias, which are a genetically and clinically heterogenous group of disorders. The panel covers genes associated with hereditary anemia, including (but not limited to) sickle cell anemia, thalassemia, Fanconi anemia, Diamond-Blackfan anemia, hemolytic anemia and pyruvate kinase deficiency. This panel is part of the Comprehensive Hematology Panel.

About Anemia

Anemia is defined as decrease in the amount of red blood cells or hemoglobin in the blood. The symptoms of anemia include fatigue, weakness, pale skin, and shortness of breath. Other more serious symptoms may occur depending on the underlying cause. The causes of anemia may be classified as impaired red blood cell (RBC) production or increased RBC destruction (hemolytic anemias). Hereditary anemia may be clinically highly variable, including mild, moderate, or severe forms. Hb Bart syndrome, that is a form of alpha thalassemias, is an example of a severe form of anemia. It is characterized by hydrops fetalis leading to death almost always in utero or shortly after birth. The thalassemias, sickle cell disease, and other hemoglobinopathies represent a major group of inherited disorders of hemoglobin synthesis (HBA1, HBA2, HBB). The thalassemias are among the most common genetic disorders worldwide, occurring more frequently in the Mediterranean region, the Indian subcontinent, Southeast Asia, and West Africa. Hereditary spherocytosis and hereditary elliptocytosis are examples of inherited hemolytic anemias. The hereditary spherocytosis is the most common congenital hemolytic anemia among Caucasians with an estimated prevalence ranging from 1:2,000 to 1:5,000.

Availability

Results in 3-4 weeks.

Genes in the Anemia Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ABCB7Anemia, sideroblastic, and spinocerebellar ataxiaXL96
ADAMTS13Schulman-Upshaw syndrome, Thrombotic thrombocytopenic purpura, familialAR22172
ALAS2Anemia, sideroblastic, Protoporphyria, erythropoieticXL2793
AMNMegaloblastic anemia-1, NorwegianAR2432
ANK1SpherocytosisAD/AR1282
ATMBreast cancer, Ataxia-TelangiectasiaAD/AR455853
ATRCutaneous telangiectasia and cancer syndrome, Seckel syndromeAD/AR613
ATRXCarpenter-Waziri syndrome, Alpha-thalassemia/mental retardation syndrome, Holmes-Gang syndrome, Juberg-Marsidi syndrome, Smith-Fineman-Myers syndrome, Mental retardation-hypotonic facies syndromeXL42149
BLMBloom syndromeAR5392
BRCA2Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familialAD/AR25141791
BRIP1Fanconi anemia, Breast cancerAD/AR8787
C15ORF41Congenital dyserythropoietic anemiaAR2
CDAN1Anemia, dyserythropoietic congenitalAR1043
CUBN*Megaloblastic anemia-1, FinnishAR3249
EPB42SpherocytosisAR912
ERCC4Fanconi anemia, Xeroderma pigmentosumAR1137
FANCAFanconi anemiaAR33474
FANCBFanconi anemiaXL714
FANCCFanconi anemiaAR3434
FANCD2*Fanconi anemiaAR1049
FANCEFanconi anemiaAR39
FANCFFanconia anemiaAR68
FANCGFanconi anemiaAR1173
FANCIFanconi anemiaAR827
FANCLFanconi anemiaAR615
FANCMFanconi anemiaAR113
G6PDGlucose-6-phosphate dehydrogenase deficiencyXL36214
GATA1Anemia, without thrombocytopenia, Thrombocytopenia with beta-thalessemia,, Dyserythropoietic anemia with thrombocytopeniaXL1614
GPIHemolytic anemia, nonspherocytic due to glucose phosphate isomerase deficiencyAD1037
GSSGlutathione synthetase deficiencyAR734
HBA1*Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia (Hemoglobin H disease)AR/Digenic8197
HBA2*Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia (Hemoglobin H disease)AR/Digenic22279
HBBSickle cell disease, Thalassemia-beta, dominant inclusion body, Other Thalassemias/Hemoglobinopathies, Beta-thalassemiaAD/AR/Digenic175835
HFEHemochromatosisAR/Digenic753
KLF1Anemia, dyserythropoietic congenital, Blood group, Lutheran inhibitorAD/BG1663
LPIN2Majeed syndromeAR810
MTRMethylmalonic acidemiaAR1139
NBNBreast cancer, Nijmegen breakage syndromeAD/AR5762
PALB2Fanconi anemia, Pancreatic cancer, Breast cancerAD/AR237223
PCPyruvate carboxylase deficiencyAR2439
PDHA1Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiencyXL39165
PDHXPyruvate dehydrogenase E3-binding protein deficiencyAR1222
PKLRPyruvate kinase deficiencyAR16240
PUS1Mitochondrial myopathy and sideroblastic anemiaAR57
RAD51CFanconi anemia, Breast-ovarian cancer, familialAD/AR4986
RPL5Diamond-Blackfan anemiaAD866
RPL11Diamond-Blackfan anemiaAD740
RPL15*Diamond-Blackfan anemiaAD22
RPL35ADiamond-Blackfan anemiaAD412
RPS7Diamond-Blackfan anemiaAD18
RPS10Diamond-Blackfan anemiaAD35
RPS17*Diamond-Blackfan anemiaAD417
RPS19Diamond-Blackfan anemiaAD9166
RPS24Diamond-Blackfan anemiaAD59
RPS26Diamond-Blackfan anemiaAD830
RPS29Diamond-Blackfan anemiaAD23
SBDS*Aplastic anemia, Shwachman-Diamond syndromeAD/AR1288
SEC23BAnemia, dyserythropoietic congenitalAR1288
SLC4A1Spherocytosis, Ovalcytosis, Renal tubular acidosis, distal, with hemolytic anemia, CryohydrocytosisAD/AR/BG30136
SLC19A2Thiamine-responsive megaloblastic anemia syndromeAR1047
SLX4Fanconi anemiaAR831
SPTA1Spherocytosis, Ellipsocytosis, PyropoikilocytosisAD/AR2145
SPTBSpherocytosis, Anemia, neonatal hemolytic, EllipsocytosisAD/AR1466
THBDThrombophilia due to thrombomodulin defect, Hemolytic uremic syndrome, atypicalAD527
TMPRSS6Iron-refractory iron deficiency anemiaAR1376
TPI1Triosephosphate isomerase deficiencyAR819
XRCC2Hereditary breast cancerAD/AR313
YARS2Myopathy, lactic acidosis, and sideroblastic anemiaAR1910
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive anemia panel that covers classical genes associated with alpha-thalassemia, beta-thalassemia, congenital dyserythropoietic anemia, congenital thrombotic thrombocytopenic purpura, Diamond-Blackfan anemia, Fanconi anemia, Grasbeck-Imerslund disease, Hb Bart's hydrops fetalis, hemoglobin H disease, hemolytic anemia, hereditary anemia, hereditary elliptocytosis, hereditary spherocytosis, shwachman-Diamond syndrome, sickle cell anemia and x-linked sideroblastic anemia. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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