title: A novel heterozygous T51I mutation of growth hormone receptor is not associated with short stature.
abstract: A novel missense mutation of the growth hormone receptor (GHR) gene was identified in a Japanese short boy with GH insensitivity. The analysis of the GHR gene revealed a novel heterozygous T51I mutation in exon 4. To clarify the effect of this mutation on GH signaling, the mutant GHR was expressed in CHO cells and its functional properties were investigated. The signal transducer and activator of transcription 5 (STAT5)-mediated transcriptional activation in mutant GHR (GHR-T51I)-expressing cells was significantly reduced as compared with wild-type GHR (GHR-wt)-expressing cells. The CHO cells co-expressing the GHR-T51I and GHR-wt, however, revealed no functional differences as compared with cells expressing GHR-wt alone, indicating that the T51I mutation does not exert the dominant negative effect. In addition, the mother and the elder brother of the proband, whose heights were normal, possessed the same heterozygous mutation. These results suggest that the heterozygous T51I mutation of GHR does not inhibit the signal transduction of GH and is not responsible for GH insensitivity.
authors.affiliation: Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sakurai
authors.forename: Keiji
authors.initials: K
authors.lastname: Iida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Kaji
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takakuwa
authors.forename: Ryou
authors.initials: R
authors.lastname: Sumita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Okimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D002648:Child; D003001:Cloning, Molecular; D006224:Cricetinae; D006580:Genetic Carrier Screening; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000235:genetics*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D011986:Receptors, Somatotropin