Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders

BMC Medical Genomics
Shanshan XuYongguo Yu

Abstract

Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES). TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patien...Continue Reading

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Citations

Jul 16, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Xiangyu ZhaoLin Li
Jun 21, 2019·Clinical Genetics·Xin LiXiumin Wang

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Methods Mentioned

BETA
exome sequencing
biopsies

Software Mentioned

PolyPhen
Swiss PDB Viewer
Clinvar
SIFT
Mutation Taster
SnpEff
GATK
BWA

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