NRAS – Cardiofaciocutaneous Syndrome

Although included in RASopathy gene panels, germline NRAS mutations have not been reported in patients with cardiofaciocutaneous (CFC) syndrome. In a comprehensive pathway analysis of five RASopathy patients (including two with CFC syndrome), no pathogenic NRAS variants were identified (PMID:20030748). Likewise, targeted NGS of 80 individuals with suspected RASopathies, encompassing CFC features, did not reveal any NRAS mutations (PMID:24451042). Somatic NRAS missense changes are well‐characterized oncogenic drivers in multiple cancers but lack evidence for haploinsufficiency or dominant‐negative effects relevant to CFC. Overall, the current genetic and experimental data support a Limited association of NRAS with CFC syndrome; additional germline studies in larger, deeply phenotyped cohorts are needed to clarify any contributory role. Key Take‐home: NRAS mutation screening has limited utility in the routine diagnosis of isolated CFC syndrome.

References

• Pediatrics international : official journal of the Japan Pediatric Society • 2010 • Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK pathway. PMID:20030748
• BMC medical genetics • 2014 • Diagnosis of Noonan syndrome and related disorders using target next generation sequencing. PMID:24451042

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