Genotypic and phenotypic characterization of Noonan syndrome: New data and review of the literature

Marjolijn Jongmans, Erik A. Sistermans, Alwin Rikken, Willy M. Nillesen, Rienk Tamminga, Michael Patton, Esther M. Maier, Marco Tartaglia, Kees Noordam, Ineke Van Der Burgt

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenpeer review

98 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)165-170
Aantal pagina's6
TijdschriftAmerican Journal of Medical Genetics
Volume134 A
Nummer van het tijdschrift2
StatusGepubliceerd - 15 apr. 2005
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Genotypic and phenotypic characterization of Noonan syndrome: New data and review of the literature'. Samen vormen ze een unieke vingerafdruk.

Citeer dit