SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype–Phenotype Correlations
2011

SOS1 Mutations in Noonan Syndrome

Sample size: 143 publication 10 minutes Evidence: moderate

Author Information

Author(s): Francesca Lepri, Alessandro De Luca, Lorenzo Stella, Cesare Rossi, Giuseppina Baldassarre, Francesca Pantaleoni, Viviana Cordeddu, Bradley J Williams, Maria L Dentici, Viviana Caputo, Serenella Venanzi, Michela Bonaguro, Ines Kavamura, Maria F Faienza, Alba Pilotta, Franco Stanzial, Francesca Faravelli, Orazio Gabrielli, Bruno Marino, Giovanni Neri, Margherita Silengo Cirillo, Giovanni B Ferrero, Isabella Torrente, Angelo Selicorni, Laura Mazzanti, Maria C Digilio, Giuseppe Zampino, Bruno Dallapiccola, Bruce D Gelb, Marco Tartaglia

Primary Institution: IRCCS Casa Sollievo della Sofferenza

Hypothesis

The study investigates the spectrum of SOS1 mutations and their associated phenotypic features in Noonan syndrome.

Conclusion

SOS1 mutations account for approximately 10% of Noonan syndrome cases and are associated with a distinctive phenotype characterized by high prevalence of ectodermal features and low occurrence of cognitive deficits.

Supporting Evidence

  • SOS1 mutations were identified in 26 of the 143 subjects (18.2%) of group 1.
  • High prevalence of ectodermal features (84%) was observed in SOS1 mutation-positive subjects.
  • Low occurrence of cognitive deficits (11%) was noted in SOS1 mutation-positive individuals.
  • Cardiac defects occurred in the majority of SOS1 mutation-positive cases (89%).
  • Fetal macrosomia was significantly higher in subjects with class 1B mutations compared to class 1A mutations.

Takeaway

This study looks at a gene called SOS1 that can cause a condition called Noonan syndrome, which affects how kids grow and develop. They found that changes in this gene are common and can lead to specific features in these kids.

Methodology

Mutation scanning of the entire SOS1 coding sequence was performed on cohorts of patients with Noonan syndrome and related conditions.

Potential Biases

Potential bias in participant selection and the reliance on clinical assessments for diagnosis.

Limitations

The study's findings may not be generalizable due to the specific cohorts analyzed and the relatively small sample size for some genotype-phenotype correlations.

Participant Demographics

The majority of participants were of European ancestry, primarily Italian.

Statistical Information

P-Value

0.024

Confidence Interval

95% CI = 0.000–0.192

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1002/humu.21492

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