Update on non-retinal genetic eye disease patients recruited from a single centre into the UK 100,000 Genomes Project

Session Details

Session Title: Presented Poster Session: New & Interesting I

Venue: Poster Village: Pod 3

First Author: : G.Karastatiras GREECE

Co Author(s): :    S. Malka   A. Webster   M. Moosajee                 

Abstract Details

Purpose:

The 100,000 Genome Project was launched in 2012 by the United Kingdom's Department of Health and Social Care, to sequence 100,000 whole genomes from national health service (NHS) patients; 50% with rare disease and 50% with cancer. Here, we provide an update on the number of genetic eye disease patients recruited from a single centre into the initiative, and report the outcomes including two example cases with congenital cataracts.

Setting:

Moorfields Eye Hospital (MEH) NHS Foundation Trust

Methods:

Recruitment into the 100,000 Genomes Project began in 2013 and ended in September 2018. Overall 85,000 people were recruited. At MEH, 1677 families consisting of 3819 individuals and 1954 affected patients were recruited over this period. The majority of families had inherited retinal diseases (1250), the remaining non-retinal genetic eye disease families included 70 with bilateral congenital cataracts, 40 with congenital glaucoma, 90 with structural globe anomalies. Results have begun to feedback, herein we present the genetic results of two non-consanguinous families with congenital cataracts who had detailed history, ophthalmic examination and relevant investigations.

Results:

A 14-year-old girl with bilateral congenital cataracts had bilateral lensectomies at age 10-12 weeks (no family history). Whole genome sequencing of the parent-offspring trio revealed a heterozygous variant in BCOR c.856del, p.(Ser286Alafs*92). Subsequent investigation revealed a unilateral left microphthalmia and abnormal dentition consistent with a diagnosis of X-linked dominant oculofaciocardiodental syndrome. A 19-year-old girl with a positive maternal history of bilateral congenital posterior polar cataracts, underwent bilateral cataract extraction and IOL implantation age 9. A heterozygous class 3 variant of unknown pathological significance was detected in CHMP4B (c.481G>C, p.[Glu161Gln]), which was later found to segregate with disease.

Conclusions:

The aim of the 100,000 Genome project is to create a new genomic medicine service for the NHS, to improve diagnostic rates and develop new and more effective treatments for patients. Through establishing a molecular diagnosis, we can ensure families have informed genetic counselling, access to family planning and referrals to the appropriate multidisciplinary team, for example, the patient with a BCOR variant, would benefit from cardiology review. Results from this project will aid the establishment of genotype-phenotype relationships and advance our knowledge of genetic eye disease.

Financial Disclosure:

None