title: Recurrent duplication mutation in HRAS causing mild Costello syndrome in a Chinese patient.
abstract: Costello syndrome (CS; OMIM 218040) is caused by heterozygous germline mutations of HRAS (OMIM 190020).We report on a patient with sporadic CS presenting with characteristic craniofacial dysmorphism, congenital cardiopulmonary disorders, intellectual impairment, and skin abnormalities manifesting as loose redundant skin of the hands and feet, acanthosis nigricans, multiple naevi and hypotrichosis. Using Sanger sequencing for the case-parents trio, we detected a de novo insertion mutation (c.187_207dup) in HRAS, which was predicted to result in duplication of amino acids 63-69 (p.E63_D69dup). This mutation was recently described in a mild case of CS, with hyperactivation of HRAS and disrupted capacity to respond to incoming signals. Our study delineates the detailed clinical features associated with this noncanonical HRAS mutation and further expands the phenotypic spectrum of CS.
authors: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: F
authors: F
authors: Xu
authors: Department of Dermatology, Peking University First Hospital, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors: H J
authors: HJ
authors: Wang
authors: Department of Dermatology, Peking University First Hospital, Beijing, China.
authors: Z M
authors: ZM
authors: Lin
authors: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: B
authors: B
authors: Yu
mesh_terms: D002675:Child, Preschool; D056685:Costello Syndrome / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)