Lead Researcher:

Dr Peter D Turnpenny

Institution:

Royal Devon & Exeter Hospital

Aim of the study:

The project aimed to use the most up-to-date molecular genetic technology, called next generation sequencing, to look for genetic causes of congenital scoliosis caused by abnormal vertebral segmentation. The Scoliosis Research Society (SRS) defines congenital scoliosis as a spinal deformity caused by vertebrae that are not properly formed during the first six weeks of embryonic development. The research group have identified a number of suitable families and their DNA will be analysed in an attempt to identify variants, and hence new genes, that are crucial to normal spine formation. If successful the findings will benefit the affected families but also provide more insights into the formation and development of the spine. This may involve collaborating with a research group in Australia who are skilled in being able to study the cell biology of the genes and their mutations in animal models.

Outcome:

The results so far are very encouraging, as follows:

– In the two families from Finland, the team found mutations (autosomal dominant inheritance, i.e. passing from one generation to the next) in a gene that has been reported previously on rare occasions. A little more work is planned and the team hope to involve Professor Sally Dunwoodie in Sydney to look into the functional manifestations of these genetic mutations. This will be of substantial interest to affected families in terms of genetic counselling and options for testing pregnancies in the event of positive findings.

– In our largest UK family with congenital scoliosis demonstrating autosomal dominant inheritance we believe we may have found the cause by identifying a mutation in a gene that has previously been implicated in a rare syndrome following autosomal recessive inheritance.  This would be a novel finding because the mechanism and mutation is different to what has previously been reported.  Again, the team are looking to involve Professor Dunwoodie for functional studies.

– In another of the UK families clearly demonstrating autosomal dominant inheritance we have identified a number of gene variants that require further analysis in order to understand their significance.  Overall, however, none of these appear to be very likely and these results may not yield anything further.