SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

Background: Heterozygous gain-of-function mutations in various
genes encoding proteins of the Ras-MAPK signalling cascade have
been identified as the genetic basis of Noonan syndrome (NS) and
cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene
encoding a guanine nucleotide exchange factor for Ras, have been
the most recent discoveries in patients with NS, but this gene has
not been studied in patients with CFCS. Methods and results: We
investigated SOS1 in a large cohort of patients with disorders of
the NS–CFCS spectrum, who had previously tested negative for
mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations
of SOS1 were discovered in 28% of patients with NS. In contrast,
none of the patients classified as having CFCS was found to carry a
pathogenic sequence change in this gene. Conclusion: We have
confirmed SOS1 as the second major gene for NS. Patients carrying
mutations in this gene have a distinctive phenotype with frequent
ectodermal anomalies such as keratosis pilaris and curly hair.
However, the clinical picture associated with SOS1 mutations is
different from that of CFCS. These findings corroborate that,
despite being caused by gainof- function mutations in molecules
belonging to the same pathway, NS and CFCS scarcely overlap
genotypically.