A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update.
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.
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Annie Ting Gee
AT
Chiu
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Gordon Ka-Chun
GK
Leung
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Yoyo Wing-Yiu
YW
Chu
Division of Medical Genetics, A.l. duPont Hospital for Children, Wilmington, Delaware.
Karen W
KW
Gripp
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Brian Hon-Yin
BH
Chung
D019943:Amino Acid Substitution; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D056685:Costello Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
Costello syndrome; HRAS mutation; RASopathy