title: A new overgrowth syndrome is due to mutations in RNF125.
abstract: Overgrowth syndromes (OGS) are a group of disorders in which all parameters of growth and physical development are above the mean for age and sex. We evaluated a series of 270 families from the Spanish Overgrowth Syndrome Registry with no known OGS. We identified one de novo deletion and three missense mutations in RNF125 in six patients from four families with overgrowth, macrocephaly, intellectual disability, mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjögren syndrome. RNF125 encodes an E3 ubiquitin ligase and is a novel gene of OGS. Our studies of the RNF125 pathway point to upregulation of RIG-I-IPS1-MDA5 and/or disruption of the PI3K-AKT and interferon signaling pathways as the putative final effectors.
authors.affiliation: CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain; Molecular Endocrinology Unit - Overgrowth Syndromes Laboratory, INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario La Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Jair
authors.initials: J
authors.lastname: Tenorio
authors.forename: Alicia
authors.initials: A
authors.lastname: Mansilla
authors.forename: María
authors.initials: M
authors.lastname: Valencia
authors.forename: Víctor
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: Valeria
authors.initials: V
authors.lastname: Romanelli
authors.forename: Pedro
authors.initials: P
authors.lastname: Arias
authors.forename: Nerea
authors.initials: N
authors.lastname: Castrejón
authors.forename: Fernando
authors.initials: F
authors.lastname: Poletta
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.forename: Gema
authors.initials: G
authors.lastname: Gordo
authors.forename: Elena
authors.initials: E
authors.lastname: Mansilla
authors.forename: Fé
authors.initials: F
authors.lastname: García-Santiago
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Casado
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.forename: María
authors.initials: M
authors.lastname: Palomares
authors.forename: María A
authors.initials: MA
authors.lastname: Mori
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos-Simarro
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández
authors.forename: Rocío
authors.initials: R
authors.lastname: Mena
authors.forename: Sara
authors.initials: S
authors.lastname: Benito-Sanz
authors.forename: Ángela
authors.initials: Á
authors.lastname: del Pozo
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Silla
authors.forename: Kristina
authors.initials: K
authors.lastname: Ibañez
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Granados
authors.forename: Alex
authors.initials: A
authors.lastname: Martín-Trujillo
authors.forename: David
authors.initials: D
authors.lastname: Montaner
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
authors.forename: Ángel
authors.initials: Á
authors.lastname: Campos-Barros
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.forename: Víctor L
authors.initials: VL
authors.lastname: Ruiz-Pérez
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
mesh_terms: D005260:Female; D006130:Growth Disorders / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012042:Registries; D013030:Spain / Q000453:epidemiology; D013577:Syndrome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C551868:RNF125 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: RNF125; autoimmune disorder; intellectual disability; macrocephaly; overgrowth