The hemoglobinopathies, molecular disease mechanisms and diagnostics.
Cornelis L HarteveldAhlem AchourSandra J G ArkesteijnJeanet Ter HuurneMaaike VerschurenSharda Bhagwandien-BisoenRianne SchaapLinda VijfhuizenHakima El IdrissiTamara T KoopmannPublished in: International journal of laboratory hematology (2022)
Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype-phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are β-thalassemia carriers presenting with features of β-thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated α-globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo-insufficiency of a non-linked gene SUPT5H on chromosome 19q, first described in two Dutch families with β-thalassemia trait without variants in the HBB gene.
Keyphrases
- copy number
- genome wide
- mitochondrial dna
- dna methylation
- end stage renal disease
- genome wide identification
- chronic kidney disease
- pregnant women
- sickle cell disease
- small molecule
- autism spectrum disorder
- newly diagnosed
- peritoneal dialysis
- risk factors
- high resolution
- prognostic factors
- mass spectrometry
- preterm birth
- intellectual disability
- single cell
- high density
- duchenne muscular dystrophy
- circulating tumor cells