Blog Posts

Marie curie Innovative training network start

9/11/2018

Our Marie Curie Innovative Training Network ‘StarT’ to diagnose, understand and treat inherited blindness is online! We're hiring brilliant PhD fellows! Please visit www.startn.eu

Save the date: Concurrent Invited Session at ASHG 2018 meeting, San Diego, October 16-20, 2018

9/10/2018

Concurrent Invited Session I, 22. Uncovering Missing Heritability in Mendelian Diseases: Lessons from Inherited Eye Diseases, ASHG 2018 meeting, San Diego, October 16-20
October 17, 10:30 AM–12:30 PM
Room 6F, Upper Level, San Diego Convention Center
Moderators: Elfride De Baere, Ghent Univ, Ghent, Belgium and Elena V. Semina, Med Col Wisconsin, Milwaukee

Eye diseases are among the most common inherited human disorders. Around one third of the known genetic defects or syndromes involve the eye. Eye research has often blazed a trail for many disciplines to follow, giving a lead in (functional) genomics, transcriptomics, genome editing, stem cell biology, animal models of disease, and the development of novel therapeutic approaches such as gene therapy. Geneticists have identified a large proportion of the genes underlying genetic eye diseases. However, the coding genetic defects identified only account for part of the morbid genome of inherited eye diseases, suggesting new classes of defects such as non-coding defects or frequent hypomorphic alleles in known or undiscovered eye disease genes. These changes are either largely undetected by conventional genomic strategies or are difficult to interpret. This session brings together a diverse group of experts in gene discovery and mechanisms of disease, bioinformatics, model systems and gene editing. They have been committed to identify genes and functionally characterize genetic defects, both coding and non-coding, that are specifically or predominantly expressed in the eye and therefore play an important role in eye function as well as in the pathogenesis of inherited eye disorders. Together, this session will address knowledge gaps in the pathogenesis of genetic eye diseases through cutting-edge approaches related to bioinformatics, (functional) genomics, genome editing and model systems as a paradigm for precision medicine in Mendelian disease.

New paper out: Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease

5/10/2018

Check out our new paper in Genetics in Medicine. You can read the abstract below, for the full text click here.

Purpose: RAX2 encodes a homeobox-containing transcription factor, in which four monoallelic pathogenic variants have been described in autosomal dominant conedominated retinal disease.
Methods: Exome sequencing in a European cohort with inherited retinal disease (IRD) (n=2086) was combined with protein structure modeling of RAX2 missense variants, bioinformatics analysis of deletion breakpoints, haplotyping of RAX2 variant c.335dup, and clinical assessment of biallelic RAX2-positive cases and carrier family members.
Results: Biallelic RAX2 sequence and structural variants were found in five unrelated European index cases, displaying non-syndromic autosomal recessive retinitis pigmentosa (ARRP) with an age of onset ranging from childhood to the mid 40s (average mid 30s). Protein structure modeling points to loss-of-function of the novel recessive missense variants and to a dominant-negative effect of the reported dominant RAX2 alleles. Structural variants were fine-mapped to disentangle their underlying mechanisms. Haplotyping of c.335dup in two cases suggests a common ancestry.
Conclusion: This study supports a role for RAX2 as novel disease gene for recessive IRD, broadening the mutation spectrum from sequence to structural variants and revealing a founder effect. The identification of biallelic RAX2 pathogenic variants in five unrelated families shows that RAX2 loss-of-function may be a non-negligible cause of IRD in unsolved ARRP cases.

PhD defence: Missing heritability in ABCA4-associated disease

19/9/2018

Miriam Bauwens defended successfully her PhD thesis on "Missing heritability in ABCA4-associated disease" on the 19th of September 2018 in Ghent. Congratulations Miriam!

New Paper Out: Revealing Cis-Regulatory elements and non-coding genetic variation

8/9/2018

Check out our latest paper published in bioRxiv. You can read the abstract below, for the full text click here.

Cis-regulatory elements (CREs) orchestrate the dynamic and diverse transcriptional programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. However, the cellular complexity of the human brain has largely precluded the identification of functional regulatory variation within the human CNS. We took advantage of the retina, a well-characterized region of the CNS with reduced cellular heterogeneity, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive resource of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines the regulatory elements with the potential to contribute to mendelian and complex disorders of human vision.

wetenschap uitgedokterd

28/8/2018

Wetenschap Uitgedokterd is een initiatief van Scriptie vzw, een non-profitorganisatie met als doel wetenschap en techniek in Vlaanderen te promoten. Opgericht in 2005 maakt Scriptie vzw er al meer dan een decennium werk van om wetenschap dichter bij de burger te brengen, dit met steun van het Departement Economie, Wetenschap en Innovatie van de Vlaamse Overheid.
Wetenschappers floreren in hun vertrouwde omgeving, of het nu gaat om hun lab, bureau of wetenschappelijke conferenties. Wetenschap Uitgedokterd haalt jonge onderzoekers uit die comfortzone en plaatst ze voor de camera met een duidelijke opdracht: deel je passie voor onderzoek met het brede publiek! Vertel ons in heldere en overtuigende 3-minuten-pitch over jouw onderzoek. Dorien, the floor is yours...

Save the date: f-TALES workshop 26-27 APRIL Leuven - Genomic Medicine

28/3/2018

Genomic Medicine is a rapidly developing science-driven approach to health care. It potentially holds great benefits for patients, clinicians, health care providers and society as a whole. The promise is on change in health care from being reactive to disease to being proactive and to predict disease onset, from being “general for all” to being “tailored to the individual”. Health care will become personalized and will change from cure to prevention, partly by limiting the burden of genetic disorders. The workshop features lectures on the technological and bio-informatic tools for genome sequencing and presents the realm and state of the art applications of Genomic Medicine.

REGISTRATION
This workshop is offered free of charge for participants, but as the number of participants is limited registration is required.
Register before 6 April 2018

VENUE
Campus Gasthuisberg
Heretraat 49 3000 Leuven
Follow the arrows ƒ-Tales to the auditorium

https://ftales.be/leuven2018/Genomicmedicine

New paper out: Functional characterization of new mutation in FTL gene causing HHCS

14/2/2018

Check out our latest paper published in Scientific Reports. You can read the abstract below, for the full text click here.

Hereditary hyperferritinaemia‑cataract syndrome (HHCS) is a rare disorder usually caused by heterozygous mutations in the iron responsive element (IRE) in the 5’ untranslated region (5’UTR) of the L‑ferritin gene (FTL), disturbing the binding of iron regulatory proteins (IRPs) and the post‑transcriptional regulation of ferritin expression. Here, the proband of a consanguineous family displayed moderate bilateral cataracts and elevated serum ferritin in the absence of iron overload. The parents and siblings showed variable degrees of mild bilateral cataracts combined with elevated levels of circulating ferritin. Sequencing of FTL identified a novel 5’UTR mutation c.-151A>G, also named “Ghent +49A>G”. The zygosity of the mutation, occurring in homozygous and heterozygous state in the proband and other affected family members respectively, correlated well with severity of ophthalmological and hematological manifestations. The substitution is expected to impair the secondary structure of the upper IRE stem. Functional characterization of +49A>G by electrophoretic mobility shift assays demonstrated a reduced binding affinity for IRP1 compared to the wild‑type IRE of FTL. Overall, we have expanded the repertoire of deleterious biallelic FTL IRE mutations in HHCS with this novel +49A>G mutation, the zygosity of which correlated well with the disease expression.

New paper out: Biallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development

22/12/2017

Check out our latest paper published in Genetics in Medicine. You can read the abstract below, for the full text click here.

Purpose: Disorders or differences of sex development (DSDs) are rare congenital conditions characterized by atypical sex development. Despite advances in genomic technologies, the molecular cause remains unknown in 50% of cases.
Methods: Homozygosity mapping and whole-exome sequencing revealed an ESR2 variant in an individual with syndromic 46,XY DSD. Additional cases with 46,XY DSD underwent whole-exome sequencing and targeted next-generation sequencing of ESR2. Functional characterization of the identified variants included luciferase assays and protein structure analysis. Gonadal ESR2 expression was assessed in human embryonic data sets and immunostaining of estrogen receptor-β (ER-β) was performed in an 8-week-old human male embryo.
Results: We identified a homozygous ESR2 variant, c.541_543del p.(Asn181del), located in the highly conserved DNA-binding domain of ER-β, in an individual with syndromic 46,XY DSD. Two additional heterozygous missense variants, c.251G>T p.(Gly84Val) and c.1277T>G p.(Leu426Arg), located in the N-terminus and the ligand-binding domain of ER-β, were found in unrelated, nonsyndromic 46,XY DSD cases. Significantly increased transcriptional activation and an impact on protein conformation were shown for the p.(Asn181del) and p.(Leu426Arg) variants. Testicular ESR2 expression was previously documented and ER-β immunostaining was positive in the developing intestine and eyes.
Conclusion: Our study supports a role for ESR2 as a novel candidate gene for 46,XY DSD.

Ophthalmic genetics journey: from Saudi Arabia to Belgium

19/12/2017

On Friday December 8 2017 Basamat ALMOALLEM, a Saudi ophthalmologist in training, successfully obtained her PhD in Health Sciences on the basis of her doctoral thesis ‘Unraveling the molecular basis of genetically heterogeneous developmental eye disorders’. Her findings unveiled examples of care valued by both patients and clinicians in the field of ophthalmic genetics. She has taken great steps towards tackling some of the challenges ophthalmic genetics is facing today.

Team photo shoot: say cheeeeeese

17/12/2017

For our new team website we obviously needed a nice team picture. The crime scene of choice was the historic centre of Ghent. We would like to thank our photographer Pieter-Jan Volders for the beautiful photos. In the picture below you can see the models getting ready for the shoot.

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