2. Academic Validation
  3. A new overgrowth syndrome is due to mutations in RNF125

A new overgrowth syndrome is due to mutations in RNF125

  • Hum Mutat. 2014 Dec;35(12):1436-41. doi: 10.1002/humu.22689.
Jair Tenorio 1,  Alicia Mansilla,  María Valencia,  Víctor Martínez-Glez,  Valeria Romanelli,  Pedro Arias,  Nerea Castrejón,  Fernando Poletta,  Encarna Guillén-Navarro,  Gema Gordo,  Elena Mansilla,  Fé García-Santiago,  Isabel González-Casado,  Elena Vallespín,  María Palomares,  María A Mori,  Fernando Santos-Simarro,  Sixto García-Miñaur,  Luis Fernández,  Rocío Mena,  Sara Benito-Sanz,  Ángela del Pozo,  Juan Carlos Silla,  Kristina Ibañez,  Eduardo López-Granados,  Alex Martín-Trujillo,  David Montaner,  SOGRI Consortium,  Karen E Heath,  Ángel Campos-Barros,  Joaquín Dopazo,  Julián Nevado,  David Monk,  Víctor L Ruiz-Pérez,  Pablo Lapunzina
Affiliations

Affiliation

  • 1 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.
PMID: 25196541 DOI: 10.1002/humu.22689
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.

Keywords

RNF125; autoimmune disorder; intellectual disability; macrocephaly; overgrowth.

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