A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update

作者：Chiu, Annie Ting Gee; Leung, Gordon Ka-Chun; Chu, Yoyo Wing-Yiu; Gripp, Karen W.; Chung, Brian Hon-Yin^*

来源：American Journal of Medical Genetics, Part A, 2017, 173(4): 1109-1114.

DOI：10.1002/ajmg.a.38118

• Costello syndrome
• HRAS mutation
• RASopathy

De novo germline mutations in HRAS cause Costello syndrome, with >95% of the mutations causing Costello syndrome affecting amino acid position 12 (p.Gly12) or 13 (p.Gly13). We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G>C: p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in <1% of patients with Costello syndrome. From literature search, there were only two other patients reported with mutations involving the same location. We summarized and updated their findings, and discussed evidence to show that these patients with less obvious signs of Costello syndrome may not necessarily run a more benign clinical course.

• 出版日期2017-4
• 单位香港大学