There has only been one study suggesting that patients with variants in HRAS have features consistent with Noonan-like syndrome with loose anagen hair (NS/LAH) (Bertola et al. 2017). This study identified five patients with sparse, loose anagen hair and p.Gly13Asp/p.Gly13Cys variants in HRAS. The authors note that no malignant tumors have been identified in these patients, however only one patient was older than 15 yrs (28 yrs) at the time of report, and it remains to be determined if the alteration of p.Gly13 in HRAS increases risk of tumor development. These patients did develop papillomata and vascular proliferation lesions as well as other features more consistent with Costello syndrome (CS), which led to the authors concluding that these cases expand the phenotypic spectrum of CS rather than support that HRAS causes NS/LAH. Therefore, the evidence for this association is Disputed. Of note, HRAS has been definitively associated with Costello syndrome. The ClinGen RASopathy Expert Panel found no evidence associating HRAS with Noonan syndrome (NS), NS with multiple lentigines, or cardiofaciocutaneous syndrome. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 7/25/18 (SOP Version 5).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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