Identification of new genetic variants responsible for Stickler Syndrome

The Stickler Syndrome encompasses several genetic diseases, which cause various eye disorders and are difficult to diagnose. For this reason, the objective of this research is to identify all the genes involved in these pathologies in order to improve the process of diagnosis and treatment.

Research team

Principal: Dr Esther Pomares

Co-researchers: Genetics Department, Dr Borja Corcóstegui (Retina and Vitreous Department) and Dr Ana Wert (Department of Pediatric Ophthalmology).


IMO Foundation's own funds


July 2019 - present

Project description

The Stickler Syndrome (STL) comprises a group of rare genetic diseases that affect the conjunctive tissue, characterized by the variable association of ocular manifestations (such as myopia, cataracts, retinal detachment or hereditary vitreoretinopathy), orofacial anomalies, osteoarticular affectations and deafness of variable severity. This pathology has an estimated population incidence ranging between 1:7500 and 1:9000 in neonates, and represents the most common hereditary cause of juvenile retinal detachment. At the genetic level, STL is caused by pathogenic variants in one of the genes responsible for the synthesis of collagens 2, 9 and 11, and in most families it is transmitted following an autosomal dominant inheritance pattern. However, recent studies have identified new genes associated with recessive forms of STL, which show the high genetic heterogeneity of this type of pathologies and open the door to the identification of possible new STL genes.

Despite the efforts to standardize the symptomatological criteria of STL, its clinical diagnosis remains a very demanding challenge, given the wide variability of phenotypic expression. In addition, other collagen diseases present very similar clinical manifestations, such as Wagner, Marshall or Donnai-Barrow syndromes. In this context, the identification of the genetic cause is crucial to confirm the specific pathology with certainty. Therefore, this project aims to identify and characterize new genes and novel genetic variants responsible for STL and other related syndromes, by studying those families with clinical pictures compatible with this type of pathologies. This analysis will be carried out using next generation sequencing, which will make it possible to determine the molecular cause, either in known genes or in genes not yet associated with STL.

Current status of the project

June 2022

The IMO Foundation research team has carried out a massive sequencing analysis of 17 families with a clinical history compatible with Stickler Syndrome and/or that present phenotypes similar to this syndrome, in order to identify the causative genetic variants in each case.In the first phase of this project, the IMO Foundation research team began recruiting 15 families with a clinical history compatible with Stickler Syndrome and other associated phenotypes for genetic analysis using massive sequencing technologies. 

To this end, the coding regions of more than 70 genes associated to date with Stickler Syndrome and other pathologies with compatible phenotypes have been studied in a total of 50 samples belonging to patients and their families. The results obtained have allowed to identify a total of 10 causal mutations in 4 different genes: COL2A1, COL11A1, LRP2 and SMAD3. Five of these mutations are new pathogenic variants and have not been previously reported in the scientific literature, so several in silico analyses of pathogenicity prediction have had to be carried out to demonstrate their possible deleterious effect. The identification of the genetic cause has allowed to corroborate the type of inheritance that presents the pathology in each family, and it has been possible to verify that 94% of the cases are of autosomal dominant inheritance.

Currently, the data obtained are still being studied, and efforts are being focused to establish the particular genotype-phenotype correlations of each candidate gene. Also, together with the team of ophthalmologists, work is being done on the establishment of basic clinical criteria for the phenotypic diagnosis of Stickler Syndrome.


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