HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation

Area of Science:

• Genetics
• Molecular Biology
• Rare Diseases

Background:

• Costello syndrome is a rare genetic disorder characterized by intellectual disability, distinct facial features, cardiovascular anomalies, tumor predisposition, and skin/musculoskeletal issues.
• Previous studies identified HRAS gene mutations in a small cohort of patients.

Purpose of the Study:

• To expand the molecular understanding of Costello syndrome by analyzing HRAS gene mutations in a larger, diverse patient group.
• To identify specific HRAS mutations associated with Costello syndrome.

Main Methods:

• Mutation analysis of the HRAS gene was performed on 40 patients diagnosed with Costello syndrome.
• Sequencing identified missense mutations within the HRAS gene.

Main Results:

• HRAS missense mutations were detected in 33 out of 40 (82.5%) patients.
• The majority of mutations occurred at codon 12 (G12S in 90.9% of mutation-positive cases), with G12A and a novel G13C mutation also identified.
• Five distinct HRAS mutations are now reported in Costello syndrome.

Conclusions:

• HRAS gene mutations are a frequent cause of Costello syndrome.
• The findings contribute to the molecular delineation of Costello syndrome, although genotype-phenotype correlations require further investigation.