Genetic causes of eye malformations
Research type
Research Study
Full title
An investigation of the genetic causes of human eye malformations
IRAS ID
199268
Contact name
David FitzPatrick
Contact email
Duration of Study in the UK
4 years, 11 months, 30 days
Research summary
Research Summary
This study aims to apply cutting edge genomic technologies to identify the cause of severe malformations affecting the eye. As such there is a requirement for biological samples and accurate phenotype (clinical) information from appropriately consented affected individuals. It is often also useful to have samples and information on family members. This is particularly important if both parents are unaffected, as trio-based genome sequence analysis (mother, father & child) has proven to be the most efficient method to identify the causative variants in a single gene.
Our study design will firstly involve identification of families and individuals affected by severe eye malformations. The participants of this study will have been referred to us from NHS clinical geneticist, genetic ophthalmologists or paediatricians with a special interest in visual impairment from the UK as well as from other countries. A formal process for obtaining written consent having been completed prior to enrolment in the study. Collection of DNA samples from the families will involve saliva samples at home or blood samples taken in clinic. A skin biopsy may rarely be requested in certain cases where we want to understand the protein product of a very rare gene mutation. Associated clinical data is also collected. All information is stored in the MRC HGU secure unit. Genetic testing via gene panel testing and whole genome sequencing is then used to determine the genetic mutation.
Our prior expectation is that a majority of severe cases will have a monogenic (single gene) cause. Using this approach we hope both to identify new variants in known genes and discover previously unrecognised causative genes. The likely causative variants will be fed-back to the participating families via their referring clinician as this may be helpful in clinical management and often clarifies the risks of recurrence within the family.
Summary of Results
Our study has identified or helped identify almost all of the genetic causes of severe eye malformations (abnormality in the shape and structure of the eye). The most common causes of anophthlamia (missing eyes) and severe microphthalmia (very small eyes) affecting both eyes is a genetic change that occurs in the baby for the first time in the gene SOX2. The same type of genetic changes also occur in in the gene OTX2. There are many other genes that can cause these eye malformations and the links to the relevant papers will be shown below.
REC name
South East Scotland REC 02
REC reference
16/SS/0201
Date of REC Opinion
8 Dec 2016
REC opinion
Further Information Favourable Opinion