Nota Clínica

RIT1: a novel gene associated with Noonan syndrome

I. Arroyo-Carrera, M. Solo de Zaldívar-Tristancho, R. Martín-Fernández, M. Vera-Torres, J.F. González de Buitrago-Amigo, J. Botet-Rodríguez [REV NEUROL 2016;63:358-362] PMID: 27699752 DOI: https://doi.org/10.33588/rn.6308.2016183

OPEN ACCESS

Volumen 63 | Number 08 | Nº of views of the article 12.641 | Nº of PDF downloads 265 | Article publication date 16/10/2016

Download PDF Castellano Citation Search in PubMed

Share in:

Go to another issue

ABSTRACT

INTRODUCTION Noonan syndrome is the most frequent of the congenital group of malformation syndromes caused by germline mutations that encode components of the RAS/MAPK pathway, termed RASopathies, one of the most frequent congenital genetic disorders in the clinical practice. Recently RIT1 mutations have been reported in patients with Noonan syndrome.

CASE REPORT A 7 years-old girl with a clinical diagnosis of Noonan syndrome, and with a hypertrophic cardiomyopathy included in her clinical manifestations, where a de novo heterozygous, probably pathogenic, novel mutation in RIT1, c.295T>C (p.Phe99Leu), has been identified.

CONCLUSIONS RIT1 shares homology with other RAS proteins and the expression of mutant alleles demonstrates a gain-of-function effect supporting a causative role in Noonan syndrome pathogenesis. Data suggest that the frequency of RIT1 mutations can be estimated as 3-5% in Noonan syndrome patients. These cases compared with Noonan patients harboring mutations in other genes are characterized by high frequency of prenatal abnormalities and hypertrophic cardiomyopathy, and lower frequencies of short stature and pectus abnormalities. We emphasize the importance of the novel identified genes in order to be included in the diagnostic panels. KeywordsDevelopmental delay Hypertrophic cardiomyopathy Noonan syndrome RAS/MAPK pathway RASopathy RIT1 CategoriesNervios periféricos, unión neuromuscular y músculo

FULL TEXT (solo disponible en lengua castellana / Only available in Spanish)

Acceso directo al último número

Último Podcast

Nota Clínica

RIT1: a novel gene associated with Noonan syndrome