title: A 3-bp deletion mutation of PTPN11 in an infant with severe Noonan syndrome including hydrops fetalis and juvenile myelomonocytic leukemia.
abstract: A de novo 3-bp deletion (179-181delGTG) was identified at exon 3 of the PTPN11 gene in a female infant with severe Noonan phenotype including hydrops fetalis and juvenile myelomonocytic leukemia. Since the 3-bp deletion is predicted to result in loss of the 60th glycine in the N-SH2 domain that is directly involved in the intramolecular interaction between the N-SH2 and the PTP domains of the PTPN11 protein, this mutation would disrupt the N-SH2/PTP binding in the absence of a phosphopeptide, leading to an excessive phosphatase activity. The results expand the spectrum of PTPN11 mutations in Noonan syndrome (NS), and suggest that a PTPN11 mutation leads to a wide range of clinical features of Noonan syndrome.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya, Tokyo 154-8567, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yoshida
authors.forename: Masafumi
authors.initials: M
authors.lastname: Miyata
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D001483:Base Sequence; D005260:Female; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics*; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D018909:src Homology Domains
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases