title: Very mild features of dysequilibrium syndrome associated with a novel VLDLR missense mutation.
abstract: Dysequilibrium syndrome (DES) is a non-progressive congenital ataxia characterized by severe intellectual deficit, truncal ataxia and markedly delayed, quadrupedal or absent ambulation. Recessive loss-of-function mutations in the very low density lipoprotein receptor (VLDLR) gene represent the most common cause of DES. Only two families have been reported harbouring homozygous missense mutations, both with a similarly severe phenotype. We report an Italian girl with very mild DES caused by the novel homozygous VLDLR missense mutation p.(C419Y). This unusually benign phenotype possibly relates to a less disruptive effect of the mutation, falling within a domain (EGF-B) not predicted as crucial for the protein function.
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Micalizzi
authors.affiliation: Child Neuropsychiatry Division, Foundation IRCCS Neurologic Institute Carlo Besta, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.affiliation: CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Ginevrino
authors.affiliation: CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Biagini
authors.affiliation: CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mazza
authors.affiliation: CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Romani
authors.affiliation: Section of Neurosciences, Department of Medicine and Surgery, University of Salerno, Via Salvador Allende, 84081, Baronissi, Salerno, Italy. enzamaria.valente@outlook.com.
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002524:Cerebellar Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL; C036053:VLDL receptor
keywords: Dysequilibrium syndrome; Next-generation sequencing; Non-progressive cerebellar ataxia; Pontocerebellar hypoplasia; VLDLR