PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome

Kenjiro Kosaki, Taichi Suzuki, Koji Muroya, Tomonobu Hasegawa, Seiji Sato, Nobutake Matsuo, Rika Kosaki, Toshiro Nagai, Yukihiro Hasegawa, Tsutomu Ogata

研究成果: Article査読

103 被引用数 (Scopus)


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 haft 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 sresult from mutations of PTPN11.

ジャーナルJournal of Clinical Endocrinology and Metabolism
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学


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