Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature.
SourceAmerican Journal of Medical Genetics. Part A, 134, 2, (2005), pp. 165-70
Article / Letter to editor
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Paediatrics - OUD tm 2017
American Journal of Medical Genetics. Part A
SubjectIGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 5: Health aging / healthy living; IGMD 8: Mitochondrial medicine; UMCN 1.2: Molecular diagnosis, prognosis and monitoring; UMCN 5.2: Endocrinology and reproduction
Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, minor facial anomalies, and congenital heart defects. In approximately 50% of cases the condition is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the protein SHP-2. In this study, PTPN11 mutation analysis was performed in 170 NS patients. In 76 (45%) of them a mutation was identified. We report on the distribution of these mutations, as well as on genotype-phenotype relationships. The benefit of the NS scoring system developed by van der Burgt et al. [(1994); Am J Med Genet 53:187-191] is shown, among physicians who consequently based their diagnosis on the NS scoring system the percentage mutation positive subjects was 54%, whereas this percentage was only 39% among physicians who made less use of the scoring system. In two patients with some uncommon manifestations mutations were found in the C-SH2 domain, a region in which defects are not often identified in NS. A trend was observed in patients carrying the 922A --> G change (Asn308Asp) receiving normal education. In one patient with NS and mild juvenile myelomonocytic leukemia (JMML) the mutation 218C --> T (Thr73Ile) was found. This confirms previous findings indicating that individuals with NS with specific mutations in PTPN11 are at risk of developing JMML.
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