A PTPN11 gene mutation (Y63C) causing Noonan syndrome is not associated with short stature in general population.
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.
Takahashi
Ikuko
I
Department of Pediatrics, Akita University School of Medicine, Japan. tomy@med.akita-u.ac.jp
Utsunomiya
Maki
M
Inoue
Kayoko
K
Takahashi
Tsutomu
T
Nozaki
Jun-Ichi
J
Wada
Yasuhiko
Y
Takada
Goro
G
Koizumi
Akio
A
D000328:Adult; D001483:Base Sequence; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007438:Introns; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009634:Noonan Syndrome / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D018909:src Homology Domains
D003062:Codon; D017027:Protein Tyrosine Phosphatases