Does the rare A172G mutation of PTPN11 gene convey a mild Noonan syndrome phenotype?
BACKGROUND
Noonan syndrome NS (OMIM 163950) is an autosomal dominant developmental disorder characterized mainly by typical facial dysmorphism, growth retardation and variable congenital heart defects. In unrelated individuals with sporadic or familial NS, heterozygous missense point mutations in the gene PTPN11 (OMIM 176876) have been confirmed, with a clustering of mutations in exons 3 and 8, the mutation A922G Asn308Asp accounting for nearly 25% of cases.


METHODS
We report a 7-year-old boy with short stature and some other clinical features of NS, who has been investigated by molecular analysis for the presence of mutations in the PTPN11 gene.


RESULTS
The de novo mutation A172G in the exon 3 of the PTPN11 gene, predicting an Asn58Asp substitution, has been found. To the best of our knowledge, this specific mutation has only been described once before, but this is the first report of detailed clinical data suggesting a mild phenotype.


CONCLUSIONS
Detailed clinical phenotype in every patient with major or minor features of NS and molecular identification of PTPN11 gene mutation may contribute to a better phenotype-genotype correlation.
Kitsiou-Tzeli
Sophia
S
Department of Medical Genetics, University of Athens, Aghia Sophia Children's Hospital, Thivon & Levadias, Goudi, Athens, Greece. skitsiou@uoa.med.gr
Papadopoulou
Anna
A
Kanaka-Gantenbein
Christina
C
Fretzayas
Andreas
A
Daskalopoulos
Dimitris
D
Kanavakis
Emmanuel
E
Nicolaidou
Polyxeni
P
D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases