Exome sequencing research has identified mutations in GATA2 in patients with primary lymphoedema and acute myeloid leukaemia (AML).
A small proportion of patients with primary lymphoedema (tissue swelling) will go on to develop a rare form of inherited AML. This is called Emberger syndrome.
Researchers from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at Guy’s and St Thomas’ and King’s College London analysed the gene sequences of eight families (14 individuals) with Emberger syndrome. The study was undertaken in collaboration with the Lymphoedema Research Group at St George’s Hospital in London.
The study identified mutations in the GATA2 gene in all the affected individuals.
Impact
“This research will help identify the small proportion of patients with primary lymphoedema who are at risk of developing AML. These patients can be closely monitored to ensure early diagnosis and treatment if they do develop AML,” says Dr Michael Simpson, a lecturer in King’s College London’s Division of Genetics and Molecular Medicine who leads the BRC's exome sequencing programme with Prof Richard Trembath.
The research also provides insight into the development and maintenance of the lymphatic system, which supports the running of other crucial body systems such as the immune and circulatory systems.
Next step
GATA2 is a ‘transcription factor’; it regulates the activity of other genes. The researchers now want to define exactly how mutations in this gene lead to lymphoedema and predispose to AML.
Research details
The research team sequenced and analysed all genes (the exome) of three unrelated individuals with Emberger syndrome. They found that all three had a mutation in the GATA2 gene.
They then sequenced the GATA2 gene in five more unrelated individuals and six family members of two of the original individuals, all affected with Emberger syndrome. All had mutations in this gene.
BRC exome sequencing programme
This study was carried out under the BRC’s exome sequencing programme. Exome sequencing is an efficient and cost-effective strategy to selectively sequence key regions of the human genome to identify genes associated with diseases.
Examples of advances made by this programme include the discovery of:
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A gene associated with pustular psoriasis
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A gene linked to possible causes of osteoporosis
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A gene that is responsible for a condition causing defects of the heart, limbs or blood vessels
P Ostergaard et al, Nature Genetics, Sept 2011
Posted on Sunday 4th September 2011