title: PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome.
abstract: Noonan syndrome is an autosomal dominant disorder defined by short stature, delayed puberty, and characteristic dysmorphic features. Tartaglia et al. (Nature Genetics, 29:465-468) have recently shown that gain-of-function mutations in the gene PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) cause Noonan syndrome in roughly half of patients that they examined. To further explore the relevance of PTPN11 mutations to the pathogenesis of Noonan syndrome, we analyzed the PTPN11 gene in 21 Japanese patients. Mutation analysis of the 15 coding exons and their flanking introns by denaturing HPLC and direct sequencing revealed six different heterozygous missense mutations (Asp61Gly, Tyr63Cys, Ala72Ser, Thr73Ile, Phe285Ser, and Asn308Asp) in seven cases (six sporadic and one familial). The mutations clustered either in the N-Src homology 2 domain or in the protein-tyrosine phosphatase domain. The clinical features of the mutation-positive and mutation-negative patients were comparable. The results provide further support to the notion that PTPN11 mutations are responsible for the development of Noonan syndrome in a substantial fraction of patients and that relatively infrequent features of Noonan syndrome, such as sensory deafness and bleeding diathesis, can also result from mutations of PTPN11.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.forename: Taichi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Sato
authors.forename: Nobutake
authors.initials: N
authors.lastname: Matsuo
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D017027:Protein Tyrosine Phosphatases