As the NHS’s medical experts in genomics, geneticists have the responsibility of keeping up to date with rapid advances, working out what’s clinically relevant, and communicating and disseminating information to colleagues across other areas of healthcare.
The launch of the new Genomic Medicine Service means that more clinicians have access to genomic tests than ever before, and clinical geneticists have an important role to play in supporting colleagues to adopt genomic testing and make use of genomic data.
In addition, the geneticist’s role in interpreting results from genomic testing – particularly in complex cases – remains vital. For more information, watch our videos with Dr Richard Scott and Dr Andrea George.
The integration of genomics expertise with other medical expertise is crucial in order to make the best use of the technology available and continue to make breakthroughs in research and treatment. Below is an example, kindly provided by Professor Gareth Evans of The University of Manchester, which demonstrates how collaboration between geneticists, oncologists, surgeons and radiologists has improved outcomes for those with Neurofibromatosis type 2.
Case study: Neurofibromatosis type 2 (NF2)
- A woman aged 27, with unilateral hearing loss and tinnitus, is diagnosed with right-sided vestibular schwannoma on brain MRI .
- On account of studies showing that such early onset can be associated with the inherited tumour predisposition syndromes NF2 and schwannomatosis, a spinal MRI was performed.
- The spinal MRI showed two further asymptomatic small nerve sheath tumours on spinal nerve roots.
- Further clinical examination showed no cutaneous features and no cataract on ophthalmic examination.
- Genetic testing was carried out and no germline pathogenic variant was identified in the NF2 or LZTR1 genes on a blood sample .
- As she had a vestibular schwannoma and two other presumed schwannomas, she met the Manchester criteria for a diagnosis of NF2.
- Absence of a germline variant in LZTR1 makes a diagnosis of schwannomatosis exceedingly unlikely and thus a presumed diagnosis of mosaic NF2 was made.
- On serial imaging, her vestibular schwannoma continued to grow, and she was discussed in the joint specialty highly-specialised NF2 service MDT, where surgery was recommended.
- She underwent a complete surgical excision of her tumour, a joint surgical procedure performed by ENT and neurosurgeons. A sample of fresh tumour was sent to the DNA laboratory.
- Genomic analysis of her tumour sample showed a c.586C>T p.Arg196X nonsense pathogenic variant in the NF2 gene at 90% allele frequency, with clear loss of the other NF2 copy on loss of heterozygosity analysis.
- Re-analysis of her lymphocyte DNA sample showed a low-level mosaicism at 1% allele frequency.
- She was advised that she had mosaic NF2 and that the gene change had occurred during development as an embryo.
- The risk to her children was of course of concern to her and we were able to advise this would be around 1%.
- Her two children, aged 10 and 8, were tested and shown not to carry the c.586C>T p.Arg196X variant, and the family was reassured that the children’s risk of NF2 was below 1 in 50,000.