There has been one reported case suggesting that Costello syndrome (CS) was caused by a de novo PTPN11 variant; however this diagnosis was made prenatally and the pregnancy was terminated (Levaillant et al., 2006). There is no further evidence supporting the pathogenicity of this variant. Furthermore, a cohort of 27 CS patients contained no PTPN11 variants. Therefore, the association is Disputed. The HRAS gene is believed to be the only gene associated with CS (Aoki et al., 2005; Estep, Tidyman, Teitell, Cotter, & Rauen, 2006; Gripp et al., 2006; Kerr et al., 2006; Zampino et al., 2007). Of note, PTPN11 has also been classified as Definitive in association with Noonan syndrome (NS) and NS with multiple lentigines and as Disputed in association with cardiofaciocutaneous syndrome. The ClinGen RASopathy Expert Panel found no evidence associating PTPN11 with NS-like disorder with loose anagen hair. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 5/31/18 (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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