title: Noonan syndrome caused by germline KRAS mutation in Taiwan: report of two patients and a review of the literature.
abstract: Noonan syndrome is a highly variable disorder that has significant phenotypic overlap with Costello syndrome and cardio-facio-cutaneous syndrome. KRAS mutation was the second reported gene for Noonan syndrome. This study screened for mutation of the KRAS gene in 57 unrelated ethnic Chinese children suffering from Noonan syndrome without PTPN11 gene mutation in Taiwan. This work only identified two patients with different missense mutations (c.40G>A, p.Val14Ile; c.108A>G, p.Ile36Met) in the exon 1 of KRAS gene. This study also analyzed the characteristics of 34 reported cases involving KRAS mutations in the literature. All these patients presented with variable phenotypes, including Noonan syndrome (n = 19), cardio-facio-cutaneous syndrome (n = 7), Costello syndrome (n = 6), and Noonan/cardio-facio-cutaneous syndrome (n = 1). The phenotype of KRAS mutations was generally severe, including short stature, mental retardation, heart defects, etc. In conclusion, this investigation demonstrates that KRAS mutations are the cause in a minority of cases of Chinese patients with Noonan syndrome in Taiwan.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, Chang Gung Memorial Hospital, Chung Gung University College of Medicine, Kweishan, Taoyuan, Taiwan. lofusu@adm.cgmh.org.tw
authors.forename: Fu-Sung
authors.initials: FS
authors.lastname: Lo
authors.forename: Ju-Li
authors.initials: JL
authors.lastname: Lin
authors.forename: Min-Tzu
authors.initials: MT
authors.lastname: Kuo
authors.forename: Pao-Chin
authors.initials: PC
authors.lastname: Chiu
authors.forename: San-Ging
authors.initials: SG
authors.lastname: Shu
authors.forename: Mei-Chyn
authors.initials: MC
authors.lastname: Chao
authors.forename: Yann-Jinn
authors.initials: YJ
authors.lastname: Lee
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009634:Noonan Syndrome / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013624:Taiwan; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins