Eye Genetics Group
Inherited eye diseases are complex and numerous group of sight-threatening conditions. The focus of the research group is a detailed clinical phenotypic characterization of genetic eye diseases, gene discovery, functional testing of variants in laboratory assays, and ultimately development treatments. We utilize up-to-date genetics methods including exome, whole-genome, and long-read sequencing. We perform chemical and cellular assays as well as use CRISPR/CAS9-technology.
Uveal melanoma genetics and BAP1 cancer syndrome: Uveal melanoma is the most common primary intraocular cancer. It metastasizes in approximately one-half of patients. For reasons unknown, the incidence of uveal melanoma is highest in northern latitudes. In Finland, all uveal melanoma patients are treated in the Helsinki University Hospital. Therefore, we have a population-wide patient collection. We have reported that 2% of Finnish uveal melanoma patients harbor a mutation in the BAP1 gene, but this explains only 25% of familial cases. Currently, we are functionally characterizing the Finnish variants in the BAP1 gene. Furthermore, we are searching for new genes predisposing to uveal melanoma using next-generation sequencing techniques.
Inherited corneal diseases: Our latest discovery is the gene behind keratitis fugax hereditaria, peculiar periodic corneal autoinflammation. The variant in the inflammasome gene NLRP3 causes this syndrome, and currently, we are functionally testing the effects of this variant in peripheral white cells, and examine potential treatments. Furthermore, we are investigating several corneal dystrophies (TGFBI-dystrophies, posterior polymorphous corneal dystrophy, Fuchs corneal dystrophy) to elucidate their genetic background in Finland
Inherited retinal diseases: Approximately 60-70% of inherited retinal dystrophies, including retinitis pigmentosa and macular dystrophy, are genetically solved. We are collecting DNA samples and phenotypic information for the large-scale discovery of new variants and genes behind genetically unsolved diseases.
Early-onset glaucoma: We are investigating the genetic background of juvenile open-angle glaucoma. We will utilize exome sequencing to identify new glaucoma genes.
Read more
Michael Backlund, PhD, senior post-doctoral researcher
Pauliina Repo PhD student
Sabita Kawan PhD student
Inka Penttinen PhD student
Perttu Liuska MD, PhD student
Annamari Immonen, PhD student, optometrist
Julia Krootila, MD student
Aleksandra Staskiewicz, MSc student
Mira Järvinen, optometrist
Annika Lipponen, research nurse
Karoliina Ahtola, research nurse
Liuska PJ, Lemmelä S, Havulinna AS, Kaarniranta K, Uusitalo H, Laivuori H, Kiiskinen T, Daly MJ, Palotie A, Turunen JA; FinnGen Consortium. Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population. JAMA Ophthalmol. 2021 Jul 1;139(7):762-768.
Augustine EF, Adams HR, de Los Reyes E, Drago K, Frazier M, Guelbert N, Laine M, Levin T, Mink JW, Nickel M, Peifer D, Schulz A, Simonati A, Topcu M, Turunen JA, Williams R, Wirrell EC, King S. Management of CLN1 Disease: International Clinical Consensus. Pediatr Neurol. 2021 Jul;120:38-51.
Jaakkola AM, Järventausta PJ, Järvinen RS, Repo P, Kivelä TT, Turunen JA. A Novel Missense TGFBI Variant p.(Ser591Phe) in a Finnish Family with Variant Lattice Corneal Dystrophy. Eur J Ophth. In press.
Liuska PJ, Harju M, Kivelä TT, Turunen JA. Prevalence of MYOC risk variants for glaucoma in different populations. Acta Ophthalmol. In press.
Repo P, Järvinen RS, Sankila EM, Paavo M, Ellonen P, Kivelä TT, Turunen JA. Identifying Haplotypes in Recessive Inherited Retinal Dystrophies Using Whole-Genome Linked-Read Sequencing. Clin Genet. Clin Genet. 2021 Jan;99(1):193-198.
Repo P, Jäntti JE, Järvinen RS, Rantala ES, Täll M, Raivio V, Kivelä TT, Turunen JA. Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma. Pigment Cell Melanoma Res. Pigment Cell Melanoma Res. 2020 Sep;33(5):756-762.
Tanigawa Y, Wainberg M, Karjalainen J, Kiiskinen T, Lemmelä S, Turunen JA, Graham R, Havulinna AS, Perola M, Palotie A, FinnGen, Daly MJ, Rivas MA. Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma. PLOS Genet. 2020 May 5;16(5):e1008682.
Turunen JA, Immonen AT, Järvinen RS, Kawan S, Repo P, Korsbäck A, Ala-Fossi O, Jaakkola AM, Majander A, Vesaluoma M, Kivelä TT. In Vivo Corneal Confocal Microscopy and Histopathology of Keratitis Fugax Hereditaria from a Pathogenic Variant in NLRP3. Am J Ophthalmol. 2020 Feb 11.
Repo P, Järvinen RS, Jäntti JE, Markkinen S, Täll M, Raivio V, Turunen JA, Kivelä TT. Population-based analysis of BAP1 germline variations in patients with uveal melanoma. Hum Mol Genet. 2019 Jul 15;28(14):2415-2426.
Walpole S, Pritchard AL, Cebulla CM, Pilarski R, Stautberg M, Davidorf FH, de la Fouchardière A, Cabaret O, Golmard L, Stoppa-Lyonnet D, Garfield E, Njauw CN, Cheung M, Turunen JA, Repo P, Järvinen RS, van Doorn R, Jager MJ, Luyten GPM, Marinkovic M, Chau C, Potrony M, Höiom V, Helgadottir H, Pastorino L, Bruno W, Andreotti V, Dalmasso B, Ciccarese G, Queirolo P, Mastracci L, Wadt K, Kiilgaard JF, Speicher MR, van Poppelen N, Kilic E, Al-Jamal RT, Dianzani I, Betti M, Bergmann C, Santagata S, Dahiya S, Taibjee S, Burke J, Poplawski N, O'Shea SJ, Newton-Bishop J, Adlard J, Adams DJ, Lane AM, Kim I, Klebe S, Racher H, Harbour JW, Nickerson ML, Murali R, Palmer JM, Howlie M, Symmons J, Hamilton H, Warrier S, Glasson W, Johansson P, Robles-Espinoza CD, Ossio R, de Klein A, Puig S, Ghiorzo P, Nielsen M, Kivelä TT, Tsao H, Testa JR, Gerami P, Stern MH, Paillerets BB, Abdel-Rahman MH, Hayward NK. Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide. J Natl Cancer Inst. 2018 Dec 1;110(12):1328-1341.
Turunen JA, Wedenoja J, Repo P, Järvinen RS, Jäntti JE, Mörtenhumer S, Riikonen AS, Lehesjoki AE, Majander A, Kivelä TT. Keratoendotheliitis Fugax Hereditaria: A Novel Cryopyrin-Associated Periodic Syndrome Caused by a Mutation in the Nucleotide-Binding Domain, Leucine-Rich Repeat Family, Pyrin Domain-Containing 3 (NLRP3) Gene. Am J Ophthalmol. 2018 Apr;188:41-50.
Turunen JA, Markkinen S, Wilska R, Saarinen S, Raivio V, Täll M, Lehesjoki AE, Kivelä TT. BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma. Ophthalmology. 2016 May;123(5):1112-7.
Tero Kivelä, MD PhD, FEBO, professor of ophthalmology
Anna Majander MD PhD, pediatric ophthalmologist
Virpi Raivio MD PhD, ocular oncologist and vitreoretinal surgeon
Minna Vesaluoma, MD PhD, cornea specialist
Kari Krootila, MD PhD, anterior segment surgeon
Mika Harju, MD PhD, professor
Hannes Lohi, PhD, professor
Maria Kaukonen, post-doctoral researcher
Heli Skottman, PhD, professor
