Document Detail

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings.
MedLine Citation:
PMID:  23321623     Owner:  NLM     Status:  MEDLINE    
In recent studies on prenatal testing for Noonan syndrome (NS) in fetuses with an increased nuchal translucency (NT) and a normal karyotype, mutations have been reported in 9-16% of cases. In this study, DNA of 75 fetuses with a normal karyotype and abnormal ultrasound findings was tested in a diagnostic setting for mutations in (a subset of) the four most commonly mutated NS genes. A de novo mutation in either PTPN11, KRAS or RAF1 was detected in 13 fetuses (17.3%). Ultrasound findings were increased NT, distended jugular lymphatic sacs (JLS), hydrothorax, renal anomalies, polyhydramnios, cystic hygroma, cardiac anomalies, hydrops fetalis and ascites. A second group, consisting of anonymized DNA of 60 other fetuses with sonographic abnormalities, was tested for mutations in 10 NS genes. In this group, five possible pathogenic mutations have been identified (in PTPN11 (n=2), RAF1, BRAF and MAP2K1 (each n=1)). We recommend prenatal testing of PTPN11, KRAS and RAF1 in pregnancies with an increased NT and at least one of the following additional features: polyhydramnios, hydrops fetalis, renal anomalies, distended JLS, hydrothorax, cardiac anomalies, cystic hygroma and ascites. If possible, mutation analysis of BRAF and MAP2K1 should be considered.
Ellen A Croonen; Willy M Nillesen; Kyra E Stuurman; Gretel Oudesluijs; Ingrid M B M van de Laar; Liesbeth Martens; Charlotte Ockeloen; Inge B Mathijssen; Marga Schepens; Martina Ruiterkamp-Versteeg; Hans Scheffer; Brigitte H W Faas; Ineke van der Burgt; Helger G Yntema
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Publication Detail:
Type:  Journal Article     Date:  2013-01-16
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-03-24     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  936-42     Citation Subset:  IM    
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MeSH Terms
Abortion, Eugenic
DNA Mutational Analysis
Molecular Diagnostic Techniques
Noonan Syndrome / genetics*,  ultrasonography
Nuchal Translucency Measurement
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-raf / genetics
ras Proteins / genetics
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC Proteins c-raf; EC protein, human; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC Proteins

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