title: Legius Syndrome: two novel mutations in the SPRED1 gene.
abstract: The SPRED1 gene encodes a protein involved in the Ras/MAPK (mitogen-activated protein kinase) signaling pathway. Mutations in SPRED1 have been reported to cause Legius Syndrome, a rare developmental disorder that shares some clinical features with Neurofibromatosis-1. Direct sequencing was used to define SPRED1 mutations. We present two previously undescribed mutations: a frameshift mutation causing a stop codon, which was identified in an Italian family (p.Ile60Tyrfs*18) and a missense variation, which was identified in one sporadic Italian case (p.Pro422Arg). Our results led us to hypothesize that these modifications may contribute to the Legius Syndrome phenotype. Further studies will be needed to determine the roles of these mutations in the mechanisms of Legius Syndrome.
authors.affiliation: Laboratory of Experimental Neurobiology, 'C. Mondino' National Neurological Institute , Pavia, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Developmental Neurology Unit, 'C. Besta' National Neurological Institute Foundation, IRCCS , Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Saletti
authors.affiliation: Child Neurology and Psychiatry Unit, Spedali Civili , Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Micheli
authors.affiliation: Developmental Neurology Unit, 'C. Besta' National Neurological Institute Foundation, IRCCS , Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Esposito
authors.affiliation: School in Reproductive and Developmental Sciences, University of Trieste , Trieste, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Molinaro
authors.affiliation: Laboratory of Experimental Neurobiology, 'C. Mondino' National Neurological Institute , Pavia, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Gagliardi
authors.affiliation: Child Neurology and Psychiatry Unit, 'C. Mondino' National Neurological Institute , Pavia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Orcesi
authors.affiliation: Laboratory of Experimental Neurobiology, 'C. Mondino' National Neurological Institute , Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda