Dragana J Josifova, Glen R Monroe, Federico Tessadori, Esther de Graaff, Bert van der Zwaag, Sarju G Mehta, Magdalena Harakalova, Karen J Duran, Sanne M C Savelberg, Isaäc J Nijman, Heinz Jungbluth, Casper C Hoogenraad, Jeroen Bakkers, Nine V Knoers, Helen V Firth, Philip L Beales, Gijs van Haaften, Mieke M van Haelst
We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation...
June 1, 2016: Human Molecular Genetics