‘Dark matter’ mutations in individuals with Stargardt disease from all over the world
In a recently published manuscript in the prestigious journal Genetics in Medicine, a large group of collaborators, led by dr. Claire-Marie Dhaenens and prof. Frans Cremers in the Department of Human Genetics in Nijmegen, the Netherlands, identified the causal mutations in the ABCA4 gene in 448 individuals with Stargardt disease (STGD1). They employed a cost-effective method, based on so-called smMIPs, to sequence the complete ABCA4 gene consisting of 128,313 base pairs. Through a semi-automated procedure, they tested more than 1,000 probands with STGD1 and allied maculopathies for the presence of causal mutations (Khan et al. Genet Med, in press).
Remarkably, they found 105 causal mutations residing in the introns of the ABCA4 gene that led to the disruptive insertion of these non-coding sequences in the messenger RNA and thus a non-functional ABCA4 protein. Among 13 novel RNA insertions identified in splicing assays, they found two intriguing complex RNA defects due to variants in introns 13 and 44. In addition, they found 16 novel large deletions, two of which were complex. Altogether, these ‘hidden mutations’ were found in 27% of the 448 genetically solved cases, illustrating the unusually high proportion of these types of mutations in STGD1.
This study was made possible through the collaboration of 75 scientists and clinicians from 21 countries from all over the world. Due to the low sequencing costs (€ 30,- per case), the research team in Nijmegen now offers this test to any individual with STGD1 or allied maculopathy in the world, at no costs, on a research basis.
This work was made possible through several grants, the most significant of which were from the RetinaUK, Fighting Blindness Ireland, Foundation Fighting Blindness USA, and the EU.
For the ITN2018 #StarT we have 1 PhD position available in the Radboudumc Nijmegen, with prof Frans Cremers. Interested to be part of an European Training Network that gives the next generation of European vision researchers unparalleled opportunities to be trained by a consortium of European vision research groups excelling in genomics, transcriptomics, functional genomics, bio-informatics, genome editing, stem cell biology, animal disease models, and therapy development; and addresses the knowledge gaps to diagnosing, understanding and treating Stargardt disease using innovative approaches related to the aforementioned disciplines?
Apply now! https://euraxess.ec.europa.eu/jobs/467487
Fighting Blindness is delighted to announce their Retina 2019 Scientific Programme will take place on Friday, November 15, 2019. Retina 2019 brings together top international and Irish researchers and clinicians in the global effort to find treatments and cures for conditions causing vision impairment and blindness. The day will include breakfast briefings, plenary discussions, poster sessions, short talks by our Young Investigators, patient perspectives and more.
Date: Friday, November 15, 2019
Time: 8:00am – 6.00pm
Location: Davenport Hotel, 8-10 Merrion Street Lower, Dublin 2.
Tickets for Retina 2019 can be purchased via www.retina.ie.
Fighting Blindness are also now accepting abstracts for poster displays and/or short talks. They welcome submissions across the wide spectrum of retinal disease and they can cover all aspects of the R&D pathway. Submissions can be made on the Retina website https://retina.ie/submit-your-abstract/
The profiles of our PhD fellows are now online!
5 PhD positions are still available! Please check out these interesting job offers.
Deadline: March 15, 2019, 17:00 CET
The deadline for applying for the 14 PhD positions December 10, 17:00 CET has passed. In case not all positions will be filled, a second round will be initiated and announced on this website.
Our Marie Curie Innovative Training Network ‘StarT’ to diagnose, understand and treat inherited blindness is online!
We're hiring brilliant PhD fellows! Please check out our job offers