Rapid Diagnosis of Rare Anemias: Novel WGS study launched at MLL
June 24, 2025
Congenital anemias, with the exception of hemoglobinopathies, are a heterogeneous group of rare genetic diseases and causes include defects in the structure, metabolism, or transport functions of erythrocytes. The various forms of hereditary anemia exhibit clinical and hematological overlaps, complicating laboratory diagnostics and differential diagnosis.
Due to the abundance of disease-causing variants in numerous genes, next-generation sequencing (NGS) has become an effective diagnostic method for hereditary anemias. This is particularly true in cases where family history is unclear or where conventional routine tests are ambigous, which often results in a significant delay in diagnosis.
Whole genome sequencing (WGS) is an unbiased approach that enables the identification of pathogenic variants in genes beyond those originally suspected at diagnosis. WGS can also detect larger genetic deletions or duplications that may remain undetected by traditional sequencing methods. For this reason, we are conducting the "WGS for Hereditary Anemias" study at MLL.
The study aims to help patients with suspected congenital anemia receive a diagnosis and treatment more quickly with the help of whole genome sequencing (WGS).
Inclusion criteria and typical clinical and laboratory findings
The following clinical and laboratory findings, as well as information
from patients' medical histories, may indicate rare congenital anemia:
- Long-standing anemia,
often known for several years
- Splenomegaly, jaundice,
and cholecystolithiasis
- Hemolysis (decreased
haptoglobin, increased LDH and bilirubin, and increased reticulocyte count)
- Hemoglobinopathy
excluded by hemoglobin differentiation and molecular genetics
- Flow cytometry:
Spherocytosis (EMA test) and paroxysmal nocturnal hemoglobinuria (PNH test) are
excluded
- Direct Coombs test is
negative (acquired anemia should be excluded)
- Positive family history
- Hereditary (hemolytic)
anemia in patients of all ages
Recruitment and study execution
If you have selected a patient for this study, please discuss
him or her with Dr. Dr. med. Armin Piehler (armin.piehler@mll.com; Tel.: +49 89
99017-357) so that we can decide together whether whole genome sequencing (WGS)
could be helpful in this case.
The necessary declarations of consent (DSGVO- and
ISO-compliant) and a registration form can be found on the study website: www.genomnet.de/wgs-bei-hereditaeren-anaemien
The patients' medical
histories and the progression of their illnesses are documented to enable
clinical evaluation. After participants are included in the study, DNA is
isolated from their peripheral blood, and whole-genome sequencing (WGS) is
performed. Then, the sequence is analyzed using the latest bioinformatics
methods. Depending on previous diagnostics, additional examinations may be
carried out, including a blood count, hemoglobinopathy diagnostics, and flow
cytometry. The Genome Network Hematology covers the costs of the WGS analysis.
Genomnet – Genome Network Hematology
The Genome Network Hematology is an association of experts who aim to use the latest genome sequencing methods to provide the best possible diagnoses and treatment options for patients with hematological diseases. The results are publicly documented and integrated into medical care. More information is available at www.genomnet.de.
The author
»Do you have questions about the study? Please feel free to send me an e-mail.«
Dr. Dr. med. Armin Piehler, PhD MM