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The majority of hematologic disorders have a genetic background. Access knowledge and testing of hundreds of single genes linked to hematologic disorder.

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Genetic testing for hematological indications

Comprehensive genetic testing and interpretation to help you diagnosing hematological disorders.


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Symptoms relate to a genetic cause

Hematological diseases primarily affect the normal function of all cell lineages derived from bone marrow particularly red blood cells (anemia; thalassemia), white blood cells and plasma cells (immunodeficiencies manifested with recurrent, severe infections) and platelets (and related clotting factors). Many of these disorders can occur as a single disorder due to mutations or can be a feature of a rare syndrome.

There are many genetic factors that play role in hematopoiesis and when they become mutated then they cause disease. Many blood disorders are recognized during the neonatal period and early childhood, and can lead to significant morbidity and mortality.

Referral reasons

  • Individuals presenting with the most common symptoms of a hematological disorder such as abnormalities in cell count numbers for different lineages (anemia, lymphopenia, neutropenia, thrombocytosis etc.), bleeding disorders, abnormal blood/bone marrow cell morphology

  • Individuals without a positive family history but with symptoms resembling the specific disease indication

  • Individuals with a negative, but suspected, family history, in order to perform genetic counseling (prenatal analyses are recommended in families of affected individuals)

Diagnostic strategy

Confirmation of a clinical diagnosis through genetic testing allows for genetic counseling and may lead to immediate medical management. For each presented case and phenotype, a full medical report will be produced including a tailored diagnostic strategy, recommendations and a differential diagnosis, if applicable.

Clinical symptoms are not always the product of the same gene or genetic variation; any diagnosis is determined as a combination of the in-depth clinical information provided and the identified genetic cause.

What do we know about hematological diseases?

Hematological diseases are a wide range of group including various different conditions, from anemias, thalassemias to autoimmune diseases, myeloproliferative diseases and metabolic conditions (please refer to the table below). The majority of hematological diseases have a genetic background and so far we know hundreds of single genes associated with hematological disorders. The causes of anemia are multifactorial, but some of the most common diseases are limited to the erythrocytes, especially the hemoglobinopathies. Hemoglobinopathies are amongst the most common monogenic diseases, with more than 1,000 different mutant alleles (mostly autosomal recessive) have been identified on the molecular level1,2. Many inherited blood conditions can be treated with the right diagnosis.

Spherocytosis are heterogeneous, inherited anemias characterized by spherical shaped erythrocytes. This disorder can be either autosomal dominant or recessive. It is the most common inherited anemia in individuals in northern European and America, where it affects about 1 in 20003.

Severe combined immunodeficiency (SCID) is a group of life-threatening genetic disorders characterized by a block in T lymphocyte differentiation that is variably associated with abnormal development of other lymphocyte lineages. At least eight diseases can be distinguished according to phenotype and inheritance pattern; the overall frequency is estimated to 1 in 75 000–100 000 births4,5. X-linked SCID accounts for 30-40% of patients with SCID6. Hematological diseases also include disorders of hemostasis, with disorders of platelets and/or coagulation proteins, typically causing excessive bleeding. Von Willebrand disease is the most common inherited bleeding disorder, with a prevalence of 1-2%7. It is normally inherited in autosomal dominant manner. Other examples include Hemophilia A and B and Congenital afibrinogenemia.

Latest Scientific Articles on Hematology

  • Spherocytosis

    Hereditary spherocytosis is a rare inherited disorder characterized by haemolytic anaemia resulting from red blood cell membrane protein anomalies. Hereditary spherocytosis is the most common inherited anemia in individuals of European ancestry, with a prevalence of 1-5 in 10,000 or higher when the…

  • Pheochromocytoma

    Pheochromocytomas (PCC) and paragangliomas (PGL) are rare catecholamine-secreting tumors that arise from the chromaffin cells of the adrenal medulla and/or from extra-adrenal sympathetic and parasympathetic paraganglia. Approximately 30% of all pheochromocytomas/paragangliomas (PGL/PCC) occur as a…

  • Afibrinogenemia

    Congenital afibrinogenemia is a rare inherited disease resulting from a defect in fibrinogen and characterized by uncontrolled bleeding. The most common manifestations of afibrinogenemia include umbilical cord bleeding, nose-bleeds (epistaxis), hemarthrosis and others. Uncontrolled bleeding in…

What can CENTOGENE do for you and your patients

CENTOGENE has identified genetic variants associated with haematological diseases in more than 115 different genes.

CENTOGENE is a global leader in the diagnosis of rare genetic diseases and has received multiple international accreditations (ISO, CAP and CLIA) that confirm the highest standards for diagnostic testing and reporting. Our experience combined with our scientific expertise and medical competence has allowed the application of state-of-the-art technologies and the development of a unique, multi-ethnic mutation database.

In CentoMD®, the world’s largest mutation database for rare diseases with 57% of unpublished variants, we have carefully created and documented all variants that have clinical relevance for related symptoms supporting the precise diagnosis of a hemetological disease.

Downloads for Hematologic disorders


Clinical findings and genetic background of the most prevalent hereditary hematological diseases

Disease Gene/Genes Clinical findings Prevalence and epidemiology Onset
Afibrinogenemia congenital FGA, FGB, FGG Most of patients with dysfibrinogenemia are asymptomatic (60%). The others may have bleeding symptoms (28%) or thrombosis (20%). 1/1,000,000 Onset at all ages
Agammaglobulinemia BTK, IGHM, BTK, IGLL1, CD79A, BLNK, LRRC8A, CD79B, PIK3R1 Recurrent bacterial infections, conjunctivitis, sinopulmonary infections, diarrhea, skin infections 3-6/1,000,000 Early onset
Bleeding disorder platelet type ACTN1, GFI1B, P2RY12 Mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma >1/1,000,000 Early onset, Adult onset
Diamond-Blackfan anemia RPS28, RPS19, RPS26, RPL26, RPL15, RPS29, TSR2, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, Pallor, weakness, failure to thrive, Growth retardation, Congenital malformations (30%-50%) 1:100,000 and 1:200,000 Age of onset: >1 year
Dyserythropoietic anemia COX4I2, C15orf41, KIF23, KLF1 Moderate to severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth retardation About 100 simplex cases (i.e., single occurrences in a family) mainly from Europe and about 70 Neonatal, childhood and rarely adult onset
Granulomatous disease CYBA, NCF2, NCF4, CYBB Severe recurrent bacterial and fungal infections, granuloma formation (pneumonia, lymphadenitis, liver abscess, osteomyelitis) 1:200,000 in US
1/111,000 in Israel Arabs
1/1,000,000 in Italy
Early to late onset
Hemolytic anemia G6PD, TPI1, CD59, KEL General pallor, tachycardia, tachypnea, hypotension, jaundice, splenomegalia 1:4,000 to 1:5,000 for HEMA
1/20,000 for HEMB9
Onset at all ages
Hemophilia F8, F9, VWF Hemarthrosis, especially with mild or no antecedent trauma, deep-muscle hematomas, prolonged bleeding after injuries 1:4,000 to 1:5,000 for HEMA
1/20,000 for HEMB9
Onset at all ages
Megaloblastic anemia AMN, CUBN Neurologic manifestations, peripheral neuropathy, dementia, subacute combined degeneration, diarrhea, macrocytosis on hematological test. 1.7% to 3.6% 1/200,000 in US high in Norway, Finland
Neutropenia ELANE, HAX1, VPS45 Recurrent fever, skin and oropharyngeal inflammation and cervical adenopathy 2-3/1,000,000 Childhood onset
Sideroblastic anemia GLRX5 Mild microcytic anemia (fatigue, breathing difficulties, weakness). For X-linked anemia (ABCB7): early-onset spinocerebellar syndrome in males, manifest primarily as delayed walking, ataxia evident in early childhood, dysmetria, and dysdiadochokinesis >1/1,000,000 Early onset, rare late onset
Sickle cell anemia HBB Shortness of breath, fatigue, and delayed growth and development in children, repeated infections, and periodic episodes of pain >1/1,00,000
1/500 African Americans
1/1,000 Hispanic Americans
Early childhood
Spherocytosis ANK1, SPTB, SPTA1, EPB42 Jaundice, splenomegaly, mild to severe anemia 1/5,000 in Europe Neonatal onset, rarely late onset
Thalassemia HBA1, HBA2, HBB, HBD Beta-thalassemia: severe anemia and hepatosplenomegaly, mild jaundice; Alpha-thalassemia: generalized fetal edema, plural/pericardial effusions 12-18% in Cyprus/Sardinia 
high in Medditeranean
Fetal to adult onset
Thrombocytopenia ANKRD26, MASTL, CYCS, ETV6, GATA1, ITGB3, ITGA2B, GATA1, WAS External bleeding (nosebleeds, bleeding gums), bruising, particularly purpura in the forearms, petechia (pinpoint bleeds in the skin and mucous membranes) 4.6-5.3/100,000 in Sweden 9,5/100,00 in US
1.6/1,00,00 worldwide
Childhood onset
von Willebrand disease VWF, GP1BA Mild mucocutaneous bleeding, bruising without recognized trauma, menorrhagia 0.1% to 1% of the population Early onset, rare late onset

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References:
  1. Old JM. Screening and genetic diagnosis of haemoglobinopathies. Scand J Clin Lab Invest.2007;67:71-86.
  2. Sonati MD, Costa FF. The genetics of blood disorders: hereditary hemoglobinopathies. Jornal de Pediatria. 2008 Aug;84(4):S40-51.
  3. Perrotta S, Gallagher PG, Mohandas N. Hereditary spherocytosis. The Lancet. 2008 Oct 24;372(9647):1411-26
  4. Fischer A, Cavazzana-Calvo M, Basile GD, DeVillartay JP, Di Santo JP, Hivroz C, Rieux-Laucat F, Le Deist F. Naturally occurring primary deficiencies of the immune system. Annual review of immunology. 1997 Apr;15(1):93-124.
  5. Picard C, Moshous D, Fischer A. The Genetic and Molecular Basis of Severe Combined Immunodeficiency. Current Pediatrics Reports. 2015 Mar 1;3(1):22-33.
  6. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ. Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993 Apr 9;73(1):147-57.
  7. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood. 1987 Feb 1;69(2):454-9.
  8. Perrotta S, Gallagher PG, Mohandas N. Hereditary spherocytosis. The Lancet. 2008 Oct 24;372(9647):1411-26

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