Tohoku J. Exp. Med., 2006, 208(3)

A PTPN11 Gene Mutation (Y63C) Causing Noonan
Syndrome is Not Associated with Short Stature in
General Population

IKUKO TAKAHASHI, MAKI UTSUNOMIYA,¹ KAYOKO INOUE,¹ TSUTOMU TAKAHASHI, JUN-ICHI NOZAKI,¹ YASUHIKO WADA,² GORO TAKADA and AKIO KOIZUMI¹

Department of Pediatrics, Akita University School of Medicine, Akita, Japan,
¹Graduate School of Medicine, Department of Health and Environment
Sciences, Kyoto University, Kyoto, Japan, and
²Department of Hygiene, Hyogo College of Medicine, Nishinomiya, Japan

Human growth is a highly complicated process, but it is obviously influenced by a genetic factor. Recent genome-wide linkage analyses suggested some genetic regions underlying stature variations. However, any specific genes underlying stature variations have not been identified. Noonan syndrome (NS) is an autosomal dominant disorder clinically characterized by short stature, minor facial anomalies, and congenital heart defects. Recently, PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) has been identified as a major responsible gene for NS, causing about half of the affected individuals. We herein report a large family demonstrating NS caused by one of the common PTPN11 mutations, c.188 A > G (Y63C). In this family, the patients were apparently healthy, but heterozygosity of the c.188 A > G (Y63C) mutation was related to growth impairment. This finding suggested that PTPN11 genetic variants contribute to adult height in the general population. However, c.188 A > G (Y63C) was not identified in 96 short individuals from the general population of 2,281 healthy adults. Thus, it is unlikely that PTPN11 is one of the genes underlying stature variations in the general population.

keywords —— Noonan syndrome; PTPN11 gene; src homology region 2-domain phosphatase-2 (SHP-2); short stature

© 2006 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2006, 208, 255-259

Received October 3, 2005; revision accepted for publication January 18, 2006.
Correspondence: Dr. Ikuko Takahashi, M.D., Department of Pediatrics, Akita University School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.

e-mail:tomy@med.akita-u.ac.jp