Genetic sequencing for investigation of perinatal mortality

• Research type

  Research Study

• Full title

  The use of exome and whole genome sequencing for perinatal mortality cases following postmortem when a structural abnormality has been identified in the baby.

• IRAS ID

  156264

• Contact name

  Mark Kilby

• Contact email

  m.d.kilby@bham.ac.uk

• Duration of Study in the UK

  2 years, 10 months, 5 days

• Research summary

  Following a perinatal mortality (or termination of pregnancy at a later gestation for a structural problem in the fetus) women and their partners are offered tests to try and identify a cause. These include a post-mortem examination to identify and confirm any structural problems. With parental consent at post-mortem a sample DNA is stored for genetic testing. Structural chromosomal anomalies leading to chromosomal copy number imbalance are often associated with perinatal mortality and morbidity.It is well described that congenital structural malformations are associated with chromosomal anomalies. The more structural abnormalities that exist in a fetus, the greater the risk of chromosome abnormality. The aim of this project is to give answers to parents as to why a structural abnormality such as a cardiac defect has occurred in their baby that is no longer living.
  Recently our group has shown that chromosomal microarray technology detects more chromosomal causes for such cases compared with traditional methods such as G-band karyotyping.However, many genetic disorders are still going undiagnosed. An extensive variety of syndromic and non-syndromic congenital anomaly phenotypes result from single gene mutations. Genome-wide sequencing, which interrogates the genome at base-pair resolution, is being trialed in the postnatal setting to provide improved genetic diagnoses for children with abnormal development, and such an approach is well-suited for the investigation of prenatally and postnatally diagnosed structural anomalies. The ability to interrogate the genome in greater resolution will significantly aid the understanding of these problems and thus improve informed management of these patients following their loss. Importantly it will allow clinicians to better establish if this is an isolated event or likely to reoccur in a future pregnancy.
  

• REC name

  West Midlands - South Birmingham Research Ethics Committee

• REC reference

  14/WM/1219

• Date of REC Opinion

  24 Nov 2014

• REC opinion

  Favourable Opinion