Group Lehesjoki

The research of our group aims at understanding the molecular basis of specific human inherited disorders through mapping and cloning of the underlying defected genes, followed by functional analyses of the gene products utilizing cellular and animal models. This will be the basis for the development of rational methods for the prevention and treatment of these disorders. Our past achievements include positional cloning of the genes underlying Progressive myoclonus epilepsy (EPM1), Northern epilepsy (CLN8), Mulibrey nanism, Cohen syndrome and Marinesco-Sjögren syndrome. Our current and future work focuses on epilepsy. Specifically, we aim to understand the molecular mechanisms underlying the two symptomatic epilepsy phenotypes, EPM1 and CLN8, and to identify genes underlying idiopathic epilepsy, including susceptibility genes for epilepsy phenotypes with complex inheritance. One main focus of the Center being in central nervous system disorders, the program on epilepsy fits well within the general frame. Moreover, as several of the disorders studied are also paroxysmal disorders that involve ion channel genes, synergy within the functional analyses can be anticipated within the Center. Finally, the group shares significant research interest with the group of Dr. Jalanko, in the characterization of the disease mechanisms of the two symptomatic epilepsy phenotypes.

MOST IMPORTANT PUBLICATIONS:
 

Virtaneva K, D'Amato E, Miao J, Koskiniemi M, Norio R, Avanzini G, Franceschetti S, Michelucci R, Tassinari CA, Omer S, Pennacchio LA, Myers RM, Dieguez-Lucena JL, Krahe R, de la Chapelle A, Lehesjoki A-E. Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1. Nature Genet 15:393-396, 1997

Lonka L, Kyttälä A, Ranta S, Jalanko A, Lehesjoki A-E. The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum. Hum Mol Genet 9:1691-7, 2000

Kallijärvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki A-E. The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: Classification of Mulibrey nanism as a new peroxisomal disorder. Am J Hum Genet  70:1215-1228, 2002

Kolehmainen J, Black GCM, Saarinen A, Chandler K, Träskelin A-L, Perveen R, Kivitie-Kallio S, Norio R, Warburg M, Fryns J-P, de la Chapelle A, Lehesjoki A-E. Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. Am J Hum Genet 72:1359-1369, 2003

Anttonen AK, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, Koenig M, Eeg-Olofsson O, Udd B, Somer M, Somer H, Lehesjoki AE. The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. Nature Genet 37:1309-1311, 2005

Siintola E, Topcu M, Aula N. Lohi H, Minassian BA, Paterson AD, Liu XQ, Wilson C, Lahtinen U, Anttonen AK, Lehesjoki AE. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet 81:136-146, 2007