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Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2005 Apr 15; Vol. 134A (2), pp. 165-70. - Publication Year :
- 2005
-
Abstract
- 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.<br /> ((c) 2005 Wiley-Liss, Inc.)
- Subjects :
- Adult
Child
Female
Gene Frequency
Genotype
Humans
Intracellular Signaling Peptides and Proteins
Male
Noonan Syndrome pathology
Phenotype
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Review Literature as Topic
SH2 Domain-Containing Protein Tyrosine Phosphatases
src Homology Domains genetics
Mutation
Noonan Syndrome genetics
Protein Tyrosine Phosphatases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4825
- Volume :
- 134A
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 15723289
- Full Text :
- https://doi.org/10.1002/ajmg.a.30598