Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth.
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.
Douglas
Jenny
J
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Cilliers
Deirdre
D
Coleman
Kim
K
Tatton-Brown
Katrina
K
Barker
Karen
K
Bernhard
Brigitte
B
Burn
John
J
Huson
Susan
S
Josifova
Dragana
D
Lacombe
Didier
D
Malik
Mohsin
M
Mansour
Sahar
S
Reid
Evan
E
Cormier-Daire
Valerie
V
Cole
Trevor
T
Rahman
Nazneen
N
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
D002352:Carrier Proteins; C522809:RNF135 protein, human; D044767:Ubiquitin-Protein Ligases