부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1399-0004.2008.01085.x Byline: KA Lee (a), BD Gelb (a,e,f,), R Kornreich (d,e,), B Williams (b), K Roza (a), H Ferguson (b), K David (c), K Eddleman (d), J Stone (d), L Edelmann (e), G Richard (b) Keywords: cystic hygroma; Noonan syndrome; nuchal translucency; PTPN11 gene analysis Abstract: Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, congenital heart defects and distinctive facies. The disorder is genetically heterogeneous with approximately 50% of patients having PTPN11 mutations. Prenatally, the diagnosis of NS has been suspected following certain ultrasound findings, such as cystic hygroma, increased nuchal translucency (NT) and hydrops fetalis. Studies of fetuses with cystic hygroma have suggested an NS prevalence of 1-3%. A retrospective review was performed to assess the utility of PTPN11 testing based on prenatal sonographic findings (n = 134). The most commonly reported indications for testing were increased NT and cystic hygroma. Analysis showed heterozygous missense mutations in 12 fetuses, corresponding to a positive test rate of 9%. PTPN11 mutations were identified in 16% and 2% of fetuses with cystic hygroma and increased NT, respectively. Among fetuses with isolated cystic hygroma, PTPN11 mutation prevalence was 11%. The mutations observed in the three fetuses with hydrops fetalis had previously been reported as somatic cancer mutations. Prenatal PTPN11 testing has diagnostic and possible prognostic properties that can aid in risk assessment and genetic counseling. As NS is genetically heterogeneous, negative PTPN11 testing cannot exclude the diagnosis and further study is warranted regarding the other NS genes. Author Affiliation: (a)Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA (b)GeneDx, Gaithersburg, MD, USA (c)Genetics Services, Department of Pediatrics, Metropolitan Hospital Center, New York, NY, USA (d)Obstetrics and Gynecology (e)Genetics and Genomic Sciences (f)Center for Molecular Cardiology, Mount Sinai School of Medicine, New York, NY, USA Article History: Received 19 May 2008, revised and accepted for publication 11 July 2008 Article note: Ruth Kornreich, PhD, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave Levy Place, PO Box 1497, New York, NY 10029, USA., Tel.: 212-241-1979; fax: 212-241-0139; , e-mail: ruth.kornreich@mssm.edu