Our group is mainly interested in the molecular genetics of retinitis pigmentosa (RP) and other retinal degenerations, a group of genetic disorders that lead to progressive loss of sight and blindness and are mostly transmitted as Mendelian traits. A peculiar feature of RP is its extreme genetic and allelic heterogeneity. Specifically, hundreds of different mutations in a few dozen genes have been so far identified as causative elements for this condition. Within this subject, we are particularly interested in the study of PRPF genes, which, if mutated, cause autosomal dominant RP.
Simulated progression of visual field loss in a patient with RP.
In collaboration with different clinical units at local University Hospital and other medical centers, we are also actively involved in genetics studies on a large spectrum of inherited diseases, ranging from congenital cardiac arrhythmias to congenital myopathies, multiple sclerosis, etc. In this context, we are performing a large-scale genetic study on the Charcot-Marie-Tooth disease, a degenerative disorder of the peripheral nervous system.
Our technical expertise encompasses all classical methods of genetic investigation, with particular emphasis to high-throughput techniques such as parallel genotyping and ultra-high throughput DNA sequencing.
Finally, we are also interested in complex disorders and participate in the Hypergenes project, a large-scale collaborative research aimed at elucidating the genetic bases of hypertension.
Recent selected publications (Complete list of publications (PubMed))
Nishiguchi KM, Tearle RG, Liu YP, Oh EC, Miyake N, Benaglio P, Harper S, Koskiniemi-Kuendig H, Venturini G, Sharon D, Koenekoop RK, Nakamura M, Kondo M, Ueno S, Yasuma TR, Beckmann JS, Ikegawa S, Matsumoto N, Terasaki H, Berson EL, Katsanis N and Rivolta C. (2013). Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. Proc Natl Acad Sci U S A 110:16139-16144.
Venturini G, Rose AM, Shah AZ, Bhattacharya SS and Rivolta C. (2012). CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance. PLoS Genet 8: e1003040.
Di Gioia SA, Letteboer SJ, Kostic C, Bandah-Rozenfeld D, Hetterschijt L, Sharon D, Arsenijevic Y, Roepman R and Rivolta C. (2012). FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies. Hum Mol Genet 21:5174-5184.
Tanackovic G, Ransijn A, Ayuso C, Harper S, Berson EL and Rivolta C. (2011). A missense mutation in PRPF6 causes impairment of pre-mRNA splicing and autosomal-dominant retinitis pigmentosa. Am J Hum Genet 88:643-649.
Tanackovic G, Ransijn A, Thibault P, Abou Elela S, Klinck R, Berson EL, Chabot B and Rivolta C. (2011). PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa. Hum Mol Genet 20:2116-21130.
Langmann T, Di Gioia SA, Rau I, Stöhr H, Maksimovic NS, Corbo JC, Renner AB, Zrenner E, Kumaramanickavel G, Karlstetter M, Arsenijevic Y, Weber BH, Gal A and Rivolta C. (2010). Nonsense mutations in FAM161A cause RP28-associated recessive retinitis pigmentosa. Am J Hum Genet 87:376-381.
Rio Frio T, McGee TL, Wade NM, Iseli C, Beckmann JS, Berson EL and Rivolta, C. (2009). A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance. Hum Mutat 30: 1340-1347.
Rio Frio T, Civic N, Ransijn A, Beckmann JS and Rivolta C. (2008). Two trans-acting eQTLs modulate the penetrance of PRPF31 mutations. Hum Mol Genet 17: 3154-3165.
Rio Frio T, Wade NM, Ransijn A, Berson EL, Beckmann JS and Rivolta, C. (2008). Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay. J Clin Invest 118: 1519-1531.