Bone Marrow Failure Syndrome 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: HE0801

The Blueprint Genetics Bone Marrow Failure Syndrome Panel is a 93 gene test for genetic diagnostics of patients with clinical suspicion of inherited bone marrow failure syndrome.

Inherited bone marrow failure syndromes are a group of clinically and genetically heterogenous disorders. The genetic diagnosis is essential in management and surveillance of these diseases. This panel comprises Congenital Neutropenia Panel, Diamond-Blackfan Anemia Panel, Fanconi Anemia Panel, Hemophagocytic Lymphohistiocytosis Panel and Hereditary Leukemia Panel. This panel is part of the Comprehensive Hematology Panel.

About Bone Marrow Failure Syndrome

Inherited bone marrow failure syndromes (IBMFS) are a diverse set of genetic disorders characterized by the inability of the bone marrow to produce sufficient circulating blood cells. Bone marrow failure can affect all blood cell lineages causing clinical symptoms similar to aplastic anemia, or be restricted to one or two blood cell lineages. The clinical presentation may include thrombocytopenia or neutropenia in some of the disorders, and hematological manifestation may be accompanied with physical features, such as short stature and abnormal skin pigmentation in Fanconi anemia and dystrophic nails, lacy reticular pigmentation, and oral leukoplakia in dyskeratosis congenita. The patients with IBMFS have an increased risk of developing cancer—either hematological or solid tumors. Early and correct disease recognition is important for management and surveillance of the diseases. Currently, accurate genetic diagnosis is essential in confirming the clinical diagnosis. The most common phenotypes that are covered by the panel are Fanconi anemia, Diamond-Blackfan anemia, dyskeratosis congenita, Shwachman-Diamond syndrome and WAS-related disorders.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Bone Marrow Failure Syndrome Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACTB*Baraitser-Winter syndromeAD2726
AK2Reticular dysgenesisAR1417
AP3B1Hermansky-Pudlak syndromeAR1423
ATMBreast cancer, Ataxia-TelangiectasiaAD/AR455853
ATRCutaneous telangiectasia and cancer syndrome, Seckel syndromeAD/AR613
BLMBloom syndromeAR5392
BLOC1S3Hermansky-Pudlak syndromeAR12
BLOC1S6Hermansky-Pudlak syndromeAR11
BRCA2Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familialAD/AR25141791
BRIP1Fanconi anemia, Breast cancerAD/AR8787
CDKN2AMelanoma, familial, Melanoma-pancreatic cancer syndromeAD37217
CEBPAAcute myeloid leukemia, familialAD129
CSF2RA*Surfactant metabolism dysfunction, pulmonaryXL214
CTC1Cerebroretinal microangiopathy with calcifications and cystsAR1329
CTSCPeriodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndromeAR1591
CXCR4Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndromeAD414
DKC1Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenitaXL4569
DTNBP1Hermansky-Pudlak syndromeAR23
ELANENeutropeniaAD30213
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
FASAutoimmune lymphoproliferative syndromeAD/AR22136
G6PC3Neutropenia, severe congenital, Dursun syndromeAR1237
GATA1Anemia, without thrombocytopenia, Thrombocytopenia with beta-thalessemia,, Dyserythropoietic anemia with thrombocytopeniaXL1614
GATA2Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, ImmunodeficiencyAD1976
HAX1Neutropenia, severe congenitalAR819
HPS1*Hermansky-Pudlak syndromeAR2641
HPS3Hermansky-Pudlak syndromeAR813
HPS4Hermansky-Pudlak syndromeAR1415
HPS5Hermansky-Pudlak syndromeAR714
HPS6Hermansky-Pudlak syndromeAR924
HRASCostello syndrome, Congenital myopathy with excess of muscle spindlesAD3026
IFNGR2ImmunodeficiencyAR418
ITKLymphoproliferative syndromeAR310
JAGN1Neutropenia, severe congenitalAR88
KRAS*Noonan syndrome, Cardiofaciocutaneous syndromeAD4638
LYSTChediak-Higashi syndromeAR4578
MAGT1Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasiaXL410
MLH1Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR6701084
MPLThrombocythemia, Amegakaryocytic thrombocytopeniaAD/AR1450
MSH2Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndromeAD/AR6461089
MSH6Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR308426
MYO5AGriscelli syndromeAR44
NBNBreast cancer, Nijmegen breakage syndromeAD/AR5762
NF1*Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndromeAD2612607
NHP2Dyskeratosis congenitaAR33
NOP10Dyskeratosis congenitaAR11
NRASNoonan syndromeAD178
PALB2Fanconi anemia, Pancreatic cancer, Breast cancerAD/AR237223
PMS2*Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR151266
PRF1Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosisAR15165
PTPN11LEOPARD syndrome, Noonan syndrome, MetachondromatosisAD122129
RAB27AGriscelli syndrome, Elejalde syndromeAR1045
RAD51CFanconi anemia, Breast-ovarian cancer, familialAD/AR4986
RECQL4Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndromeAR3492
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
RTEL1Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenitaAD/AR2726
RUNX1Platelet disorder, familial, with associated myeloid malignancyAD1374
SBDS*Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasiaAD/AR1288
SH2D1ALymphoproliferative syndromeXL14120
SLX4Fanconi anemiaAR831
STX11Hemophagocytic lymphohistiocytosis, familialAR515
STXBP2Hemophagocytic lymphohistiocytosis, familialAR860
TCIRG1Osteopetrosis, severe neonatal or infantile forms (OPTB1)AR9127
TERCAplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenitaAD3660
TERTAplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenitaAD/AR39133
TINF2Revesz syndrome, Dyskeratosis congenitaAD2033
TP53Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Breast cancer, familial, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphomaAD148391
UNC13DHemophagocytic lymphohistiocytosis, familialAR9139
USB1Poikiloderma with neutropeniaAR421
WASNeutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndromeXL32429
WRAP53Dyskeratosis congenitaAR56
XIAP*Lymphoproliferative syndromeXL478
XRCC2Hereditary breast cancerAD/AR313
  • * 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 bone marrow failure syndrome panel that covers classical genes associated with Bloom syndrome, Diamond-Blackfan anemia, dyskeratosis congenita, ELANE-related neutropenia, familial hemophagocytic lymphohistiocytosis, Fanconi anemia, Hermansky-Pudlak syndrome, inherited bone marrow failure syndrome, severe congenital neutropenia, shwachman-Diamond syndrome and Wiskott-Aldrich syndrome. 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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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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