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USING Knowledge | 19
Deciphering
genetic disease
The DECIPHER database is benefiting
patients, clinicians and researchers.
2 3 4
vision of two remained stable while that
of the third improved significantly –
possibly because the disease was at an
earlier stage of progression.
Though preliminary, these findings –
along with those from a similar trial
carried out in the USA – justify trials in
children with less advanced
degeneration and greater potential for
benefit.
Bainbridge JW et al. Effect of gene therapy on visual
function in Leber’s congenital amaurosis. N Engl J Med
2008;358(21):2231–9.
The gene therapy trial was funded by the
Department of Health, the National Institute of
Health Research Biomedical Research Centre
for Ophthalmology and the British Retinitis
Pigmentosa Society.
Chromosomal rearrangements are a
common cause of developmental
conditions in young infants. The
DECIPHER database, set up by Nigel
Carter at the Wellcome Trust Sanger
Institute and Helen Firth in
Cambridge, enables clinicians and
researchers worldwide to pool
knowledge about the causes and
consequences of these conditions.
Dr Carter has pioneered the development
of tools that can search the entire human
genome for copy number variation –
regions that have been duplicated or
lost. These alterations are a common
cause of developmental conditions.
Traditional methods of diagnosis rely on
microscopic analysis of chromosomes,
but cannot spot subtle changes.
Dr Carter teamed up with Dr Firth, a
clinical geneticist at Addenbrooke’s
Hospital in Cambridge, to develop the
DECIPHER database so new findings
emerging from the use of genomic tools
could be shared globally. As conditions
may be extremely rare, the global reach
can be particularly valuable. For example,
the database enabled researchers to
identify a syndrome caused by a small
deletion on chromosome 17. A similar
cluster of cases – two from Vancouver,
Canada, and one from Cambridge –
revealed a new syndrome linked to loss
of part of chromosome 14.
Connecting cases this way can reassure
clinicians that the genetic change detected
is directly linked to the condition –
everyone has some shuffled DNA, most
of it harmless. Information can also be
shared on the progression of disease.
Researchers can use the information to
investigate genes in the affected regions
and how their loss or duplication might
cause the condition.
Parents also benefit from a diagnosis. As
well as being able to guide clinical care, a
diagnosis can be comforting – parents at
last have an explanation for their child’s
condition and can be reassured that they
were not in any way to blame. It may also
reveal whether they are at risk of having
another affected child.
Since it was set up in 2004, more than
100 centres have registered with
DECIPHER. More generally, genomic
analysis has been taken up by many
medical genetic centres as an adjunct to
conventional methods. And at least one
centre has already abandoned the
microscope in favour of DNA-based tools.
Zahir F et al. Novel deletions of 14q11.2 associated with
developmental delay, cognitive impairment and similar
minor anomalies in three children. J Med Genet
2007;44;556–61.
Shaw-Smith C et al. Microdeletion encompassing
MAPT at chromosome 17q21.3 is associated with
developmental delay and learning disability. Nat Genet
2006;38;1032–7.