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Clinical and molecular spectra of BRAF-associated RASopathy

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Abstract
Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are the most common subtypes of RASopathy. As an effector of Ras, BRAF is one of the molecules responsible for RASopathy. We investigated the phenotypic and genotypic features of 26 patients with BRAF-associated RASopathy. The clinical diagnoses were CFC (n = 21, 80.8%), NS (n = 3, 11.5%), NS/CFC (n = 1, 3.8%), and undefined syndromic intellectual disability (ID) (n = 1, 3.8%). The mostly shared phenotypes were ID (90.5%), cutaneous manifestations (84.6%), congenital heart defects (76.9%), short stature (76.9%), and dysmorphic features such as short neck (65.4%) and low-set ears (65.4%). Importantly, moderate to severe ID (57.1%) and epilepsy (26.9%) were noted. Eighteen different missense mutations were found, including a novel mutation, p.Phe498Tyr. p.Gln257Arg (n = 9, 34.6%) was the most common mutation, and the mutations were clustered in the cysteine-rich domain or protein kinase domain. A review of previously reported cases along with our findings revealed the existence of multiple sub-phenotypes of RASopathy within a single genotype, indicating that BRAF-associated RASopathy is not variant-specific. Our study further delineated the diverse and expanded clinical phenotypes of BRAF-associated RASopathy with their molecular genetic characteristics.
Author(s)
고정민금창원김구환서고훈유한욱이범희이예나전종근전지현최윤하최인희최진호
Issued Date
2021
Type
Article
Keyword
AdolescentChildChildPreschoolEctodermal Dysplasia / geneticsEctodermal Dysplasia / pathology*FaciesFailure to Thrive / geneticsFailure to Thrive / pathology*FemaleHeart DefectsCongenital / geneticsHeart DefectsCongenital / pathology*HumansInfantMaleMutation*|\Noonan Syndrome / geneticsNoonan Syndrome / pathology*PhenotypeProto-Oncogene Proteins B-raf / genetics*
DOI
10.1038/s10038-020-00852-3
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7593
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2449992579&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Clinical%20and%20molecular%20spectra%20of%20BRAF-associated%20RASopathy&offset=0&pcAvailability=true
Publisher
JOURNAL OF HUMAN GENETICS
Location
일본
Language
영어
ISSN
1434-5161
Citation Volume
66
Citation Number
4
Citation Start Page
389
Citation End Page
399
Appears in Collections:
Medicine > Medicine
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