RT Journal Article SR Electronic T1 Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 401 OP 405 DO 10.1136/jmg.2005.040352 VO 43 IS 5 A1 B Kerr A1 M-A Delrue A1 S Sigaudy A1 R Perveen A1 M Marche A1 I Burgelin A1 M Stef A1 B Tang A1 O B Eden A1 J O’Sullivan A1 A De Sandre-Giovannoli A1 W Reardon A1 C Brewer A1 C Bennett A1 O Quarell A1 E M’Cann A1 D Donnai A1 F Stewart A1 R Hennekam A1 H Cavé A1 A Verloes A1 N Philip A1 D Lacombe A1 N Levy A1 B Arveiler A1 G Black YR 2006 UL http://jmg.bmj.com/content/43/5/401.abstract AB Background: Costello syndrome (CS) is a rare multiple congenital abnormality syndrome, associated with failure to thrive and developmental delay. One of the more distinctive features in childhood is the development of facial warts, often nasolabial and in other moist body surfaces. Individuals with CS have an increased risk of malignancy, suggested to be about 17%. Recently, mutations in the HRAS gene on chromosome 11p13.3 have been found to cause CS. Methods: We report here the results of HRAS analysis in 43 individuals with a clinical diagnosis of CS. Results: Mutations were found in 37 (86%) of patients. Analysis of parental DNA samples was possible in 16 cases for both parents and in three cases for one parent, and confirmed the mutations as de novo in all of these cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases. Conclusions: These results confirm that CS is caused, in most cases, by heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major phenotypic features by mutation suggests a potential correlation between malignancy risk and genotype, which is highest for patients with an uncommon (G12A) substitution. These results confirm that mutation testing for HRAS is a reliable diagnostic test for CS.