Molecular causes of primary angle-closure glaucoma
Zusammenfassung der Projektergebnisse
Primary angle closure glaucoma (PACG) is the second most common form of glaucoma and affects at least 16 million people globally. Up to date, no disease causing gene for PACG has been reported. Since the last funding period, we have investigated the genetic mechanism of PACG using the strategy of family based linkage analysis combining with whole exome sequencing. Some promising candidate loci for PACG have been discovered. From the collected 200 families we selected 59 most informative families with 288 individuals for genotyping. We did not find specific linkage regions with classically defined phenotypes. Considering the specific anatomical features of the studied disorder, we created one scoring system for better defining the phenotypes, and with the refining phenotypes, we revealed several suggestive linkage regions. To reduce the complexity of the disorder, we further carried out linkage analysis with different intermediate phenotypes and detected several suggestive linkage regions respectively, among them, two genomic regions (chr1p36 and chr3q25-28) always overlapped in different analysis, which was set as the highest priority for the following exome sequencing analysis. From exome sequencing of four families, we discovered 23 variants in total based on the detected linkage regions and the gene functions involved in the eye development. We evaluated the 23 variants in a 1065 PACG patient and 623 control cohorts and finally 12 candidates are defined to be the most promising disease causing genes. We analyzed the discovered candidate genes together for the protein-protein interaction and found many of them interacted with each other, indicating that these genes belong to the same molecular pathway.
Projektbezogene Publikationen (Auswahl)
- Two novel GATA6 mutations cause childhood-onset diabetes mellitus, pancreas malformation and congenital heart disease. Horm Res Paediatr. 2013;79(4):250-6
Gong M, Simaite D, Kühnen P, Heldmann M, Spagnoli F, Blankenstein O, Hübner N, Hussain K, Raile K
(Siehe online unter https://doi.org/10.1159/000348844) - Recessive mutations in PCBD1 cause a new type of early-onset diabetes. Diabetes. 2014 May 21 [Epub ahead of print]
Simaite D, Kofent J, Gong M, Rüschendorf F, Jia S, Arn P, Bentler K, Ellaway C, Kühnen P, Hoffmann GF, Blau N, Spagnoli FM, Hübner N, Raile K
(Siehe online unter https://doi.org/10.2337/db13-1784)
