title: Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth.
abstract: 17q11 microdeletions that encompass NF1 cause 5%-10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is within the NF1 microdeletion region, in six families characterized by overgrowth, learning disability, dysmorphic features and variable additional features. These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Douglas
authors.forename: Deirdre
authors.initials: D
authors.lastname: Cilliers
authors.forename: Kim
authors.initials: K
authors.lastname: Coleman
authors.forename: Katrina
authors.initials: K
authors.lastname: Tatton-Brown
authors.forename: Karen
authors.initials: K
authors.lastname: Barker
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bernhard
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: Susan
authors.initials: S
authors.lastname: Huson
authors.forename: Dragana
authors.initials: D
authors.lastname: Josifova
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Mohsin
authors.initials: M
authors.lastname: Malik
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.forename: Evan
authors.initials: E
authors.lastname: Reid
authors.forename: Valerie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; C522809:RNF135 protein, human; D044767:Ubiquitin-Protein Ligases