Previous studies of CFC1 (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal function of this protein is required for proper laterality development in humans.
The results showed no abnormalities in the coding region of the PTPN11 gene in any CFC patient, nor any evidence of major deletions within the gene suggesting that mutations in other gene(s) are responsible for this syndrome.
The genetic cause of CFC syndrome remains unknown, and PTPN11 can be reasonably excluded as a candidate gene for the CFC syndrome, which we regard as molecular evidence that CFC and Noonan syndromes are distinct genetic entities.
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome.
With our previous exclusion of PTPN11 mutations in CFC syndrome, these data suggest distinct genetic etiologies for Noonan, CFC and Costello syndromes.
Finally, due to phenotypic overlap between CS and cardio-facio-cutaneous (CFC) syndromes, the HRAS coding region was sequenced in a well-characterized CFC cohort.